FutureMedicine Magazine

₹ 250.00 VOL 5 | ISSUE 6 PAGES 100 OCTOBER 2018 FUTUREMEDICINEINDIA.COM

NON-INVASIVE PRENATAL SCREENING ENTERS EXCITING FRONTIERS

KNOWING

THE UNBORN

REGULATORY

DIAGNOSTICS

COMBO-DRUGS ON THEIR WAY OUT?

MICRODELETION: LOST IN TRANSLATION

HEAD & NECK CANCER

CASE REPORT

ORAL CANCER STAGING BY DEPTH OF INVASION

HOW SHE REGAINED HER LOST TASTE

editor’s note

AUGUST 2018 OCTOBER 2018/ / Vol: Vol.55/ / Issue: Issue 4 6

Founder Editor Founder & & Editor CH Unnikrishnan CH Unnikrishnan Executive Editor Executive Editor SS Harachand Harachand

Science Editor Science Editor Dr Rajanikant Vangala

Dr Rajanikant Vangala

Consulting Editors Copy Editor Shah Dr Shivanee Sreejiraj D’Silva Eluvangal Jeetha Dr Sumit Ghoshal Consulting Editors Copy Editor Dr Shivanee Shah Sreejiraj Eluvangal Dr Sumit Ghoshal Correspondent Photo Editor Divya Umesh Choyikutty Goswami

Photo Editor Illustrator Umesh Goswami

Mathewkutty J Mattam

Design Editor Advisory BoardK Gopakumar

Dr Devi Shetty

Illustrator Dr B S Ajaikumar J Mattam Mathewkutty

Dr Shashank Joshi

Advisory Board S Dr Prof. Arumugam Dr Devi Shetty Dr I C Varma Dr B S Ajaikumar Dr NShashank K Warrier Joshi Dr Dr Sekar Dr Prof. Seshagiri Arumugam S Dr I C Verma Knowledge Partner Dr N K Warrier SGRF Dr Sekar Seshagiri Business Head Mr Rajesh R Nair

Tushar KanchanPartner Knowledge SGRF Circulation & Subscription Manager S Sanjeev Nair Business Head Tushar Design &Kanchan Graphics

Circulation & Subscription Manager Blackboard Kochi S Sanjeev Nair

Dear Doctor, Dear Doctor Needless to say, you, and every other honest healthcare provider truly hold a respectable position the society.

This respect nothing We know you are busy.

It is in always reassuring that theistrust and but faiththe of reflection of the trust that men and women in the society have in you as hundreds of patients in your healing touch keeps you busy in this noble the custodian of their health. So, naturally, it comes to you with its own profession. In the hectic practice, it’s quite natural that you might miss share of responsibilities. In this era of transformative science and research, out on some of the latest developments in emerging medicine. In this era the responsibility has a much larger context that goes beyond mere sickof innovation, medical science is getting redefined almost by the day. Old care. It also includes the care of the health of the society, which will in turn technologies are being replaced by the new in the blink of an eye. Robots determine the future progress of humanity. and artificial intelligence are taking over a good part of the procedures, As Future Medicine always stressed in its mission, we want to seamlessly while genomics and molecular science unveil the mysteries of life further. connect the researcher with the doctor, bridging the gap between them. It We are fortunate to have such breakthroughs as they help specialists like is the time to translate the benefits of that knowledge to the society at large you rise above of today’s informed patient. in the form of athe realexpectations transformation.

And that is the real responsibility which you, as a new age clinician, share.

Similarly, it isknow, also a time burden when India is witnessing revolutionary As we all India’s of non-communicable diseases growth is risingin healthcare industry, especially in the private sector, wherein an increasing rapidly. The country’s peculiar and complex population groups and their number of doctors up multiple rolesRecent of clinician, researcherinand genetics add to the are loadtaking of inherited ailments. advancements entrepreneur.

This requires expansion of your focus to a wider canvas.

In human genomics have proven to be capable of tracing the genesis of many this context, it becomes important how a busy professional like you can of these diseases accurately, and to control them to a great extent. But keep pace withthe these latest developments in a quick and easy way. unfortunately, awareness about such advanced technologies, including parental and prenatal screening and testing that can help take informed At Future before Medicine, which is conceived and crafted by a team of senior decisions birth, is still very poor in India. journalists, scientists and doctors, our look aim is help you docrucial just that.

We of We, in this issue, are taking a closer atto the country’s burden are equipped to bring youmyths the latest theabout science care technologies from across genetic disorders and the and from realities theoflatest the world in an interesting and convenient way, supplemented the best that the country can take advantage of in this regard, along withby many other breakthroughs and developments in the in field of medicine practice. of views and analyses from the masters each field. We and present you this specialised knowledge vehicle that plugs you into the emerging world of Happy reading, care seamlessly. Come, let’s join hands in this information journey.

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FutureMedIndia

AUGUST 2018/ FUTURE MEDICINE / 3

Vol 5 Issue 6 October 2018

₹ 250.00 VOL 5 | ISSUE 6 PAGES 100 OCTOBER 2018 FUTUREMEDICINEINDIA.COM

28 NON-INVASIVE PRENATAL SCREENING ENTERS EXCITING FRONTIERS

KNOWING

THE UNBORN

REGULATORY

DIAGNOSTICS

COMBO-DRUGS ON THEIR WAY OUT?

MICRODELETION: LOST IN TRANSLATION

HEAD & NECK CANCER

CASE REPORT

ORAL CANCER STAGING BY DEPTH OF INVASION

HOW SHE REGAINED HER LOST TASTE

DIAGNOSITCS

LOST IN TRANSLATION Microdeletion syndrome is one of a frequently unsuspected group of disorders in prenatal evaluation

REGULAR FEATURES

06 Letters 08 News updates 12 Research 32 Drug approvals 48 Education 60 Research snippets 62 Pharma 64 Hospital news 66 Head & neck cancer 68 Insurance 70 Health care 72 Public health 74 Medico legal 80 Devices 86 Products 90 Events 96 Calendar 97 Book review 98 Holy grail

54

14

CASE REPORTS

RESEARCH

SLEEP-ONSET SEIZURE

PRETERM RISK HIGHER WITH ART: STUDY

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

Lack of surveillance and the absence of procedural guidelines are leading to an alarming rise in ART-linked preterm births

38 REGULATORY

FDCS ON THEIR WAY OUT? India slaps ban on 328 drug combos finding no therapeutic justification for the ingredients contained

76

ETHICS

DOCTORS OWE A CONSTITUTIONAL DUTY TO TREAT THE HAVE-NOTS: SC

Test results must aid clinical decision-making and should be beneficial to patients.

Maximilian Schmid M.D.

Head of Medical Affairs, Roche Sequencing Solutions, California

44

STRAIGHT TALK

“INDIA WILL SOON MAKE THAT BIG REVOLUTION OF CHEAPER ROBOTIC SURGERY”

16

COVER STORY

KNOWING THE UNBORN Non-invasive, cfDNA-based approach opens exciting frontiers in prenatal genetic probe

letters to the editor ₹ 250.00 VOL 5 | ISSUE 5 PAGES 100 SEPTEMBER 2018 FUTUREMEDICINEINDIA.COM

CUTTING-EDGE ADVANCES IN INTERVENTIONAL TECHNOLOGY ARE TAKING CARDIOVASCULAR MEDICINE BY STORM

TRANSCATHETER

TRANSFORMATION

CARDIOGENETICS

CASE REPORT

EDUCATION

ONCOLOGY

INHERITED CVD: BIGGEST KILLER GETS OFF SCOT-FREE

HEART RHYTHM DISORDERS MIMIC EPILEPSY

DNBs SEEK EQUIVALENCE WITH MD

GINGIVO-BUCCAL CANCERS ARE DIFFERENT

Nicely done Hi, Received the September edition. Useful contents and nicely done. Congrats.

Dr Hisham Ahmed Consultant cardiologist Armrita Institute of Medical Science, Kochi.

Excellent Concept Hello, It is a great attempt to create

a fusion of pure science and clinical practice, which is also presented in an interesting way. Doctors will enjoy reading this. Excellent concept.

Prof. Bhaskar D Goolab Dept. of Obstretics &Gynaecology University of Witwatersrand, Johannesburg, SA.

Business insights Dr Moopen’s views on hospital entrepreneurship was really insightful.

Dr Raju Patil Vasai Polyclinic, Maharshtra

Insightful Dear Sir, Read your September edition. The interview with Dr Moopen was really insightful as far as preparation for healthcare startup is concerned. His concerns about unupdated medical curriculum in India is true

and hope the MCI and other authorities listens to it.

Dr Jayathilakan Anna Salai, Chennai-02

heart diseases and modern procedures. As a practicing cardiologist, enjoyed reading the same. As reported, the inherited heart diseases is still a serious crisis in India, which is yet to get adequately addressed.

Dr Vasudev Shirodkar Shirodkar Clinic, Mumbai

Really good

Fresh look

Hello, I think I must comment on the cover story of the September edition of FM.It is really good. Very topical.

I appreciate the way you choose the topics. Ovearll, the layout of the magazine looks excellent!. Keep it up.

Cheers, Dr Manish Kakodkar, Worli Seaface, Mumbai

Hi Sir, Cover story on less-invasive technologies was interesting.

Looking forward to more such tech-based articles. Also, the magazine has got a fresh look with excellent cover theme and design.

Dr. Jhanvi Shankar Nagesh Bangalore

Serious crisis Dear Editor, The September edition was a good package on the

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news updates

India brings HIV/AIDS Act into force I ndia's health ministry has enforced the Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome (Prevention and Control) Act, 2017 with effect from September 10, 2018.

The Act, which aims to safeguard the rights of people living with HIV and affected by HIV, has provisions to address HIVrelated discrimination, strengthen the existing anti-discrimination programme by bringing in legal accountability and establish formal mechanisms for inquiring into complaints and redressing grievances.

Seeking to prevent and control the spread of HIV and AIDS, the Act lists various grounds on which discrimination against HIV positive persons and those living with them

Online pharmacy Netmeds raises Rs 247 cr

O

Online pharmacy Netmeds has raised $35 million (Rs 247 crore) from Southeast Asian business group Daun Penh Cambodia Group based in Singapore, a company statement said.

Existing investors Sistema Asia Fund, the venture capital fund of Russian conglomerate Sistema JSFC, and Tanncam Investment, a Cambodian investment holding company, also put in money in

this round, the statement added.

Netmeds is planning to use the new funds to increase awareness through marketing efforts as well as to enhance customer experience, reports said, quoting company sources.

The company had, in October last year, raised $14 million from Tanncam and Sistema Asia Fund.

Promoted by Dadha & Company, Netmeds provides a wide range of medicines listed under various categories, along with OTC products including wellness products, vitamins, diet/fitness supplements, herbal products, pain

8 / FUTURE MEDICINE / OCTOBER 2018

is prohibited. These include the denial, termination, discontinuation or unfair treatment with regard to: (i) employment, (ii) educational establishments, (iii) health care services, (iv) residing or renting property, (v) standing for public or private office, and (vi) provision of insurance.

The requirement for HIV testing as a prerequisite for obtaining employment or accessing health care or education is also prohibited.

Every HIV infected or affected person below the age of 18 years has the right to reside in a shared household and enjoy the facilities of the household. The Act also prohibits any individual from publishing information or advocating feelings of hatred against HIV positive persons and those living with them.

relievers, diabetic care kits, baby/mother care products, beauty care products and surgical supplies.

Dr Poonam Khetrapal gets 2nd term at WHO

D

r Poonam Khetrapal Singh has been nominated as regional director of WHO South-East Asia for a second five-year term.

The 11 member countries of WHO South-East Asia Region, which met at the regional committee session to elect the next regional director, selected Dr Khetrapal Singh unanimously, reports said.

Dr Khetrapal Singh’s current term started on 1 February 2014. During the period, she identified seven flagship priorities -– achieving universal health coverage; strengthening emergency response capacity; reversing

non-communicable disease epidemics; finishing off neglected tropical diseases; combating antimicrobial resistance; preventing maternal, under-five and neonatal deaths, eliminating measles and controlling rubella. She further added eliminating tuberculosis as her eighth flagship in 2017.

The region, which was certified polio-free in 2014, continues to maintain this status. It also succeeded in eliminating maternal and neonatal tetanus,

becoming only the second WHO region to do so. The region could also bring down the maternal mortality rates by 69 per cent.

Dr Khetrapal's next fiveyear term will begin on 1 February 2019.

EU partners with India to develop flu vaccine

T

he European Union (EU) joined hands with India on research and innovation to develop a next-generation influenza vaccine.

EUR 30 million has been earmarked for the research and development activity with the objective of advancing the efficacy, safety, duration of immunity and reactivity against a large number of influenza strains.

Both the EU and the Department of Biotechnology (DBT), Government of India, have committed EUR 15 million each to fund the joint project. The EU fund for this programme comes from its research and innovation 'Horizon 2020' programme.

These joint efforts also aim to develop cost-effective and affordable influenza vaccine rapidly without compromising quality. Keeping this in mind, the participating consortia need to bring together multidisciplinary stakeholders who can represent any part of the chain from the lab to the market.

seasonal flu vaccination is also high on the EU health agenda with the European Commission urging EU member states to commit to vaccinating 75% of risk groups against seasonal flu each year.

Health ministry asks states to ban e-cigarettes

I

ndia's health ministry has asked states to ban Electronic Nicotine Delivery Systems (ENDS), including e-cigarettes, vape, e-sheesha, e-hookah etc..

“As such, the states/ Union Territories are advised, in larger public health interest and in order to prevent the initiation of ENDS by non-smokers and youth with special attention to vulnerable groups, to ensure that any Electronic Nicotine Delivery Systems (ENDS) including e-cigarettes, heatnot-burn devices, vape, e-sheesha, e-nicotine flavoured hookah,” according to an advisory issued by the ministry.

These devices enabled nicotine delivery

“In engaging jointly on this topic, India and the EU are contributing to an important global public health challenge.

Improved influenza vaccines would help the international

and hence should not be sold either online or offline. The advisory also stated that these should not be manufactured, distributed, traded, imported and advertised in the state jurisdictions, except for the purpose and in the manner and to the extent as may be approved under the Drugs and Cosmetics Act, 1940 and the rules made thereunder.

The Indian states of Punjab, Karnataka, Kerala, Mizoram, Jammu and Kashmir, Uttar Pradesh and Bihar have already prohibited the use of e-cigarettes and have prohibited the manufacture, import, sale and distribution of ENDS, reports said.

Govt may change labelling for fluoroquinolones

T

community to better prepare in the event of an influenza pandemic,” said Tomasz Kozlowski, Ambassador of the European Union, launching the programme.

It is expected that the outcome of the projects will also contribute to the achievement of Sustainable Development Goal 3 to ensure health and well-being for all and boost the Indian National Health Mission. Addressing

he Central Drugs Standard Control Organisation (CDSCO), India's top drug regulator, is planning to change the labelling norms for fluoroquinolone class of antibiotics. The intended change is to bolster the warnings about the risks of mental health side-effects and serious blood sugar fluctuations.

The proposed regulation is close in line with a similar action taken by the US Food and Drug Administration.The US drug regulator announced safety labelling changes to make warnings more consistent across the labelling for all fluoroquinolones taken by mouth or given by injection.

India's Minister of State for Health and Family Welfare, Anupriya Patel stated in Parliament that “in view of the action of US FDA on labelling changes of fluoroquinolones, the Drug Controller General of India is examining the issue in consultation with subject expert committee of CDSCO”.

The list of fluoroquinolones approved by US FDA include levofloxacin, ciprofloxacin (Cipro), ciprofloxacin extended-

OCTOBER 2018 / FUTURE MEDICINE / 9

BC Roy awards go to three doctors from Lucknow T

hree leading doctors from Lucknow were conferred with the country's prestigious BC Roy awards.

SGPGI director Prof Rakesh Kapoor and KGMU Vice-Chancellor Prof MLB Bhatt have been awarded as ‘eminent medical teacher’. Dr Deepak Agarwal, gastroenterologist, has been awarded ‘to recognise the best talents in development of specialities in different branches in medicine’ for his contributions to gastroenterology, stated a press release from the Medical Council of India.

Prof Bhatt, who was part of Operation Meghdoot launched by the Indian Army in 1984 to capture the Siachen Glacier, did his graduation from KGMU and joined the Indian Army’s medical corps under the Short Service Commission.

He later did his masters in radiotherapy and started

release tablets, moxifloxacin ofloxacin, gemifloxacin and delafloxacin.

The US agency went on to insist labelling changes following a recent review that found instances of hypoglycemic coma where users of fluoroquinolones experienced hypoglycemia.

The US FDA first added a Boxed Warning to fluoroquinolones in July 2008 for the increased risk of tendinitis and tendon rupture.

Dr K K Aggarwal is pres-elect of CMAAO

P

adma Shri Awardee Dr K K Aggarwal has been elected as the president-elect of Confederation of Medical Associations of Asia and

Prof Rakesh Kapoor

Prof MLB Bhatt

Dr Deepak Agarwal

teaching. He served as KGMU medical superintendent in 2006-07. He was appointed the Vice-Chancellor of KGMU in 2017. In the area of medical research, Prof Bhatt has been instrumental in developing original biomarkers for testing oral, breast, and urinary bladder cancers.

Prof Rakesh Kapoor was the winner of the prestigious Hewett Medal in graduation.

Also an alumnus of KGMU,

Prof Kapoor joined SGPGI Chandigarh for superspeciality in urology. In 1988, he became a faculty at SGPGI Lucknow.

A gold medallist in masters in general surgery, Prof Kapoor is credited with developing new vaginoplasty techniques wherein a vagina is created from a section of the small intestine to help women born without ovaries and vagina.

Dr Deepak Agarwal is an expert in endoscopic

ultrasound, laparoscopic surgery and gastric bypass surgery.

The BC Roy Award, considered the highest medical honour in the country, is given in five categories. The award to eminent medical teachers includes Rs 15,000 and a medal for each awardee.

The selections are made by a managing committee appointed by the Medical Council of India.

an advisor to the ethics committee, World Medical Association.

Dr Aggarwal, who is currently the president of Heart Care Foundation Of India (HCFI), was elected to CMAAO at the 2018 General Assembly held at Penang, Malaysia.

Oceania (CMAAO).

CMAAO represents 19 member National Medical Associations (NMAs).

Dr Aggarwal will take charge as the president of CMAAO on September 5, 2019 at Goa. A leading cardiologist, Dr Aggarwal was the past national president of the Indian Medical Association (IMA) and the first vice president of CMAAO and

10 / FUTURE MEDICINE / OCTOBER 2018

docprime. com gets $50m internal fund

d

ocprime.com, an online medical services provider promoted by EtechAces Marketing and Consulting Private Limited (Policybazaar Group), has received initial internal infusion of US$ 50 million from the parent company.

Presently, docprime.com is

associated with 14,000 doctors and 5,000 diagnostic labs. The online medical portal plans to expand its network to 1,50,000 doctors and 20,000 labs across over 100 cities, according to the company.

The online booking of appointments are currently restricted to doctors and labs located in Delhi-NCR, but the facility will be made available across all major cities including Mumbai, Bengaluru, Hyderabad & Chennai from next month onwards. docprime. com, a venture by the Policybazaar Group, connects patients with doctors in real time through stateof-the-art technology and a robust offline network.

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research

CANCER VAC TO COMBAT LYNCH Indian researchers discover that a personalised vaccine could well address a hereditary form of colorectal cancer

A

recent study by Bengaluru-based genetics research and diagnostics player MedGenome has found that a cancer vaccine would be the answer for personalized treatment for Lynch Syndrome (LS), a hereditary nonpolyposis colorectal cancer (HNPCC).

Lynch Syndrome, one of the most common hereditary syndromes, increases the lifetime risk of developing cancers of other organs, such as colon, stomach, small intestines, liver, kidney, uterus, brain, pelvis and prostate.

MedGenome, in collaboration with Kailash Cancer Hospital and Research Center (KCHRC), Goraj, examined the feasibility of treating Lynch Syndrome using a personalized cancer vaccine approach by identifying potential immunogenic tumour specific alterations.

The company used its proprietary neoepitope prioritization pipeline - OncoPeptVAC - to select potential immunogenic peptides from wholeexome and RNA-seq data generated from patient tumour. From a list of over 50 predicted neoepitopes, three neoepitopes were tested in an ex vivo CD8+ T cell activation assay confirming their immunogenicity.

Explaining the working of this potential vaccine treatment, Amit Chaudhuri, Vice-President, R&D at MedGenome, said since cancer mutations are recognized by the body’s immune system as foreign, tumour cells carrying these mutations are often eliminated. So, it is often very challenging to predict which mutations are potentially immunogenic. The answer to such challenging conditions are good cancer vaccines.

MedGenome has built a bioinformatic pipeline to predict potential cancer vaccines by analysing a patient’s tumour using next generation

12 / FUTURE MEDICINE / OCTOBER 2018

SCREENING FOR GENETIC MUTATION IN COLORECTAL CANCER PATIENTS, ESPECIALLY THOSE WITH A FAMILIAL HISTORY, COULD HELP IN IDENTIFYING THOSE THAT ARE VULNERABLE TO THE DISEASE.

sequencing. The process involves sequencing tumour DNA to identify all cancer mutations, using RNA sequencing data to ascertain the mutations that are expressed by the tumour cells, and analysing the properties of the mutated amino acid to predict whether it will be recognized by the T cell receptor.

In the lynch syndrome study, the patient’s tumour contained over 900 cancer mutations, of which about 50 were predicted to be immunogenic - which means that these mutations or neoepitopes were predicted to be recognized by the T cells to mount an immune response. Three predicted neoepitopes were tested in an assay and were found to activate T cells, validating that the prediction was

correct. These three neoepitopes can be used as vaccines for treating the patient. It is likely that many of the 50 predicted epitopes will also be immunogenic, although it was not tested in the experiment. The assay is time consuming, laborious and requires specialized skill-sets to perform.

According to Dr. Rakshit Shah, surgical oncologist, KCHRC, Vadodara, the screening for genetic mutation in colorectal cancer patients, especially those with a familial history, could help in identifying those that are vulnerable to the disease.

“Such genetic-based screening could be an efficient way of preventing colorectal cancer. Families with history of colorectal cancer like Lynch syndrome should be advised to undergo genetic screening and if they carry mutations like MLH1, they are likely to develop the disease before the age of 50. “Our study is unique, as genetic screening in familial colorectal cancer has not been widely reported in India,” he added.

“Given that Lynch syndrome has limited treatment options, this study provides a basis for considering a cancer vaccine approach that could be used either as monotherapy or in combination with established immunooncology or chemotherapy drugs,” said Dr. Amit Chaudhuri, who co-authored the study.

Talking about the potential development of the vaccine, Dr Chaudhuri added that the company’s pipeline is the front-end of a long chain of processes that will lead to a product that can be given to the patient. “A big challenge is GMP manufacturing of peptides for individual patients, and formulating the peptides with appropriate adjuvants so that the vaccines can evoke a strong immune response in the patient.,” he added.

AUGUST 2018/ FUTURE MEDICINE / 85

research

PRETERM RISK HIGHER WITH ART: STUDY Lack of surveillance and the absence of procedural guidelines are leading to an alarming rise in ART-linked preterm births JEETHA D’SILVA

A

dvances in reproductive technology have benefited many women, but it is only recently that the collateral risks involved in these procedures have come to light. A recent study conducted among 113 women in Mumbai found that the incidence of preterm births was alarmingly high in women who have conceived through Assisted Reproductive Technology (ART).

The study, conducted by the National Institute for Research in Reproductive Health (NIRRH) and the Indian Council of Medical Research (ICMR), found that 76.23% of such women had preterm deliveries. Pregnancy related

14 / FUTURE MEDICINE / OCTOBER 2018

complications like pre-eclampsia (15%), gestational diabetes (11%) and heterotopic pregnancy (3%) were also found to be significantly high in this cohort.

Dr Anushree Patil, scientist, NIRRH, and the lead author of the study said that the higher incidence of preterm births was mostly due to the increase in pregnancies among women over the age of 35 years and the fact that most ART procedures have higher order multiple births.

“The profile of most of the patients who come in for ART procedures puts them at high risk. The average age is above 37 and many of them have been treated for fibroids and/or diabetes and other conditions. In addition, some of

them may have undergone previous surgeries because of which the risk of preterm deliveries is higher,” says Dr Ameet Patki, medical director, Fertility Associates, and the past secretary general of Indian Society for Assisted Reproduction (ISAR).

Of the 113 women who were part of the study, 51 women (45.1%) had antepartum haemorrhage. Out of these, 45 women (35.9%) had bleeding episodes during the 1st trimester, of which four sustained pregnancy losses. Ten women had bleeding episodes during the second trimester, five of which were terminated. All the women were given progesterone supplementation to support the pregnancy till 12 weeks of pregnancy.

18 women (15.9%) required the use of tocolytic agents to arrest or prevent preterm labor in the late second and early third trimester.

Multiple gestations were observed in 51 participants (45.1%) and singleton pregnancies in 62 participants (54.9%). The high incidence of multiple gestations can be correlated with the high incidence of preterm births observed in this study.

INCIDENCE OF PRETERM BIRTHS HIGHER IN INDIA

Higher in India The World Health Organization reports that about 15 million babies – or around 10 percent – are born prematurely around the world every year. In India, the incidence is higher. According to the National Health Portal, preterm births account for about 13% of all births in India. Preterm births are a significant health problem. Complications due to preterm birth is the leading cause of mortality in neonates, accounting for almost 1 million deaths worldwide each year.

Besides, preterm babies that survive might require prolonged neonatal intensive care and are at a greater risk of severe impairment and morbidities such as cerebral palsy, sensory deficits, learning disabilities and respiratory illnesses. The cost associated with providing medical care and support to preterm babies could run into several lakhs, and could hence be well out of the reach of many people.

“When you talk to couples who wish to undergo ART, it is important to counsel them and inform them about the risks. Providing medical care for a baby that is born preterm could be financially draining as the cost could be between Rs 10,000 to Rs 15,000 a day,” said Dr Patki.

It is also important that these pregnancies are closely supervised.

With ART clinics coming up in smaller cities and towns, more people now have access to these procedures, but these mofussil areas often do not have the infrastructure to care for babies that are born preterm. “We also need to create awareness. We now have a test – called the fibronectin test – which costs approximately Rs 4,000,

10%

13%

WORLD

INDIA

15

million through which we can ascertain the risk of preterm deliveries. Patients who show a higher risk can be identified and managed appropriately,” he added.

In addition, administering betamethasone as a prophylactic in the seventh month helps to accelerate lung maturity in the foetus so this can

ART CLINICS ARE COMING UP IN SMALLER CITIES AND TOWNS. BUT MOFUSSIL AREAS OFTEN DO NOT HAVE THE INFRASTRUCTURE TO CARE OF BABIES THAT ARE BORN PRETERM.

greatly reduce complications in babies that are born preterm. In case of the early onset of labour in high-risk cases in remote areas, medicines should be given as early as possible to slow down the process, and the patient should be transferred to a medical centre that is equipped with NICU facilities to provide optimum care for the neonate, Dr Patki added.

Lacking data The findings of the Mumbai study, the first of its kind in India, are similar to

babies are born prematurely around the world in a year The WHO reports

those of such studies conducted in the West. However, as the researchers point out, there is lack of data in the Indian context, unlike in the West where such pregnancies are extensively documented. “The Centre for Disease Control in Atlanta has very detailed records of such pregnancies, which make it easier for researchers to study the data,” Dr Patil said, emphasising the need for setting up a robust surveillance system in India.

“With the growing use of ART, there is a strong need to develop a National ART surveillance system in India like the one in CDC Atlanta. Mechanisms need to be built into the reporting systems like the National ART Registry of India to get complete data on the pregnancy course and outcomes of ART conceptions,” the researchers stated in their study.

The researchers also called for the formulation of guidelines for ART procedures. With multi-foetal pregnancies being very common in assisted reproductive technologies, the risk of preterm deliveries is also subsequently higher. “In most ART procedures, multiple embryos are transferred. This often leads to multifoetal pregnancies which could itself lead to preterm deliveries. Hence, there is a need to restrict the number of embryos that are transferred. This needs to be done at the policy level,” Dr Patil said.

OCTOBER 2018 / FUTURE MEDICINE / 15

cover story

KNOWING

UNBORN

THE

Non-invasive, cfDNA-based approach opens exciting frontiers in prenatal genetic probe

16 / FUTURE MEDICINE / OCTOBER 2018

S HARACHAND

T

he trajectory to determine the risk of foetal abnormalities of genetic origin has been made a lot simpler and safer for clinicians today with the advent of non-invasive prenatal testing (NIPT).

Till a few years ago, the detection and diagnosis of autosomal aneuploidies involved a multi-step process. The combined first-trimester screening (FTS) to assess the risk comprises the analysis of the pregnancy-associated plasma protein A and the free beta-human chorionic gonadotropin in the maternal blood, plus an ultrasound measuring foetal nuchal translucency (NT) thickness. The detection rate of the two biochemical marker analysis, in combination with NT ultrasound, has only been around 75%, with 5% false positives.

A positive finding invariably led to invasive procedures like amniocentesis or chorionic villus sampling (CVS) to confirm the diagnosis. Extraction of foetal samples for genetic evaluation causes considerable distress to both the unborn foetus and the pregnant woman. Besides, the method itself carries a risk of miscarriage, especially when carried out in locations where expertise and facilities are inadequate.

Genomic abnormalities are the leading cause of birth OCTOBER 2018 / FUTURE MEDICINE / 17

says Maximilian Schmid, MD, Head of Medical Affairs, Roche defects, including foetal growth retardation and pregnancy Sequencing Solutions, California. Roche’s Harmony prenatal test complications. NIPT, in a technological breakthrough, now to detect trisomy 21, 18 and 13 is currently available in more makes it possible to determine the genomic status of the than 100 countries, with more than 1.4 million patient samples foetus by analysing the circulating foetal DNA in the maternal tested, he adds. blood.

NIPT has a sensitivity of 99% and a specificity of 99.92% Expanding potential for trisomy 21, which detects Down’s syndrome and nearly similar level of accuracy for trisomy 18 and trisomy 13 -- the Recent advances in genome sequencing have broadened common autosomal aneuploidies. the scope of NIPT further. Going by the trend, disorders Cell-free foetal DNA, or the DNA of placental origin, of monogenic origin are logically the next in line. comprises less than 10% of the DNA in the blood of a pregnant Hemoglobinopathies such as thalassaemia and sickle cell woman. The ’foetal fraction’ analysis can anaemia are already brought under its be done earlier than any other pregnancy purview. Since the principle of cfDNA involves screening or diagnosis. It helps to complete the analysis of the entire foetal genome testing formalities earlier in those receiving a in maternal plasma, NIPT can, technically, THE ’FOETAL FRACTION’ negative result. As a sufficiently informative look beyond chromosomal abnormalities ANALYSIS CAN BE DONE to Mendelian disorders and genetic risk test with better accuracy, it obviates the EARLIER THAN ANY need for other investigations. profiles for multifactorial diseases, studies The increased level of sensitivity and say. There is, virtually, no limit to the number OTHER PREGNANCY specificity in detecting aneuploidies makes of diseases and conditions that can be SCREENING NIPT a better option for patients and predicted through the technology.

OR DIAGNOSIS. clinicians. Even though its use is currently Leading companies have already limited to screening purposes and not for expanded their panel portfolio to include diagnosing, several countries, including the microdeletion syndromes like DiGeorge.

Netherlands, have already implemented NIPT as a part of their “Deletion of 22q11.2 is the second most common national prenatal screening programme. identifiable genetic cause of developmental delay and major Evidence from studies conducted in low-risk, general congenital heart disease after Down syndrome. Occurring populations shows that NIPT can be considered an in as many as 1/1,000 pregnancies, it is the most common alternative to the current first-tier testing for first-semester microdeletion syndrome,” according to Dr Schmid. prenatal screening in many healthcare settings. Also, there As demonstrated with 22q11.2 deletion, Roche will are indications that the number of invasive foetal tests has continue to focus on adding clinically meaningful content to its decreased considerably since the introduction of NIPT in many test offerings, he added. parts of the world, including in the US and Australia. Many NIPT is the best technology that is available today for women who previously would have had invasive testing are screening chromosomal disorders in pregnancy, and it is being choosing NIPT because of the small risk of pregnancy loss. recommended by obstetric and gynaecological societies the ”NIPT has seen unprecedented, rapid clinical adoption world over, points out Dr. Priya Kadam, Programme Director with studies showing a decrease in both the number of - NIPT, MedGenome Labs, a genomics-based research and traditional screening tests and invasive diagnostic procedures,’’ diagnostics company from Bengaluru.

DOWN‘S DETECTION NIPT has a sensitivity of 99% and a specificity of 99.92% for trisomy 21, which detects Down’s syndrome.

Population risk set at

1/800

False-positive rate of FTS

4.8%

DETECTION RATE T21 FTS/NT scan

NIPT

73%

99%

False-positive rate of NIPT:

< 0.1%

Iatrogenic miscarriage: miscarriage due to invasive procedures

1%

18 / FUTURE MEDICINE / OCTOBER 2018

NIPT AVAILABLE IN INDIA*

According to Dr Kadam, it would be a better idea to have all pregnant women go through NIPT irrespective of their risk profile because genomic changes in the foetus can occur due to many factors. For instance, spontaneous chromosomal disorders, which is the most common type of chromosomal disorder, including Down’s syndrome, Edwards syndrome and 22q or DiGeorge syndrome, occurs during the pregnancy sans any previous family history. “In this case, not even the parents are carriers. The changes are spontaneous. It is important to note that in the case of family history or suspected genetic mutation in parents, one will be careful or cautious about the pregnancy. But, so far as spontaneous disorders are concerned, there is no alert factor, so it is recommended that every pregnancy should be screened for certain chromosomal disorders,” she explained At present, India has several tests available for detecting almost all the disorders.

Of late, companies have even started marketing tests that track down single point mutation disorders in India.

According to Dr Shailesh Pande, Consultant-HOD, Dept. of Medical Genetics, Metropolis Healthcare Ltd, a wide range of maternal serum screening test from dual marker to NIPS are available. Proper genetic counselling and appropriate test selection can really help to identify at risk population for foetal chromosomal abnormalities.

Addressing awareness gap Even as genomic advances have significantly improved screening and diagnosis of chromosomal conditions prenatally, they have also created new challenges for health professionals and families.

The growing number of available tests are likely to have positive effects on prenatal care. However, the level of awareness about them among patients and providers continues to impede their uptake.

“Obstetricians have poor awareness of foetal therapy

Down’s syndrome (trisomy 21) Edward’s syndrome (trisomy 18) Patau syndrome (trisomy 13) Cri-du-chat syndrome (5p minus syndrome) Wolf-Hirschhorn syndrome (deletion 4p syndrome) Jacobsen syndrome (11q deletion disorder) Klinefelter’s syndrome (presence of an additional X chromosome in males) Turner syndrome ( presence of only a single X chromosome in females) XYY syndrome XXX syndrome

Obstetricians have poor awareness of foetal therapy conditions and tend not to advise patients correctly.

Certain monogenic disorders *List incomplete

Dr Anita Kaul

Clinical Director, Apollo Centre for Fetal Medicine, New Delhi OCTOBER 2018 / FUTURE MEDICINE / 19

IMPROVING GENETIC QUOTIENT Genetic screening to enable health assessment today for healthy tomorrow DR RAJANIKANTH VANGALA

E

mpowering a mother is enabling a brighter future for the country.

A major goal of clinicians is to bring down maternal mortality and premature births and do prenatal defect detection.

This goal can be achieved by prenatal screening for birth defects, which, until recently, required invasive methods like collecting amniotic fluid, which contains foetal cells -- mostly of epithelial origin -- or chorionic villus samples, which have mesodermal connective tissue and trophoblastic cells of the placenta.

These invasive techniques do carry a greater risk, including that of foetal loss.

However, the increasing knowledge about circulating cell-free fetal DNA (ccffDNA) and its presence in the mother’s blood has led to the development of noninvasive prenatal screening or testing (NIPS or NIPT). Every human being carries cell-free DNA. However, pregnant women carry around 10-15% ccffDNA, depending on several factors such as the inverse association with an increase in maternal weight. These ccffDNA fractions from each chromosome can help in identifying specific genetic aspects or defects in the foetus. For example, statistically significant higher levels of DNA fragments from chromosome 21 correlate with trisomy 21 (Down syndrome). The small amounts of DNA fragments are further analyzed in bioinformatics by comparing them with reference human genome to identify anomalies. Cost-effective, targeted

sequencing has been developed now, for example, for chromosomes 13, 18, 21, X and Y.

Adhering to guidelines NIPS was introduced in India in 2012 and is now spreading quickly in all major cities. There are approximately 26 million births every year in India and NIPS could truly help improve health systems.

WHILE NIPS MAY SOON BECOME POPULAR IN CITIES IN INDIA, THE PENETRATION OF RURAL AREAS WILL BE A HUGE HURDLE AS EVEN BASIC MEDICAL SERVICES ARE YET TO BE MADE UBIQUITOUS THERE.

However, it is imperative that medical specialists and obstetricians be aware of the relevant recommendations and guidelines so that the test can be used properly. Based on the guidelines of American College of Medical Genetics and Genomics (ACMG), NIPS has been limited to screening assessments and is not used for diagnostics. This suggests that there may be potential residual risk of disease, albeit very low, even if the test comes back normal. However, this is true in case of any other biochemical or ultrasound

conditions and tend not to advise patients correctly,’’ says Dr Anita Kaul, Clinical Director, Apollo Centre for Fetal Medicine, New Delhi. The ever-increasing possibilities of genetic screening also make doctors a bit uncertain.

“As doctors, we are not reassuring the patients in the way we used to, because we always keep saying that you haven’t done all the possible tests that can be run on this foetus, so we cannot allay your anxiety completely.’’

Earlier, the obstetrician could order for a karyotyping and inform the patient that “we’ve done the only genetic test 20 / FUTURE MEDICINE / OCTOBER 2018

study. This aspect must be explained to the patient clearly. Would-be parents and family in India may expect these tests to be 100% accurate, like in the case of invasive tests such as amniocentesis and chorionic villi tests. The recommendations and guidelines must be adhered to in explaining the scientific rationale of such tests, and probably, a simplified metaanalysis of relevant studies could be presented to the patient.

One of the most important factors in a healthy pregnancy is the age of mother at the time of giving birth. In India, the proportion of women who are greater than 35 years of age at the time of delivery is increasing to 2-5%. The second important factor to be considered is the high rate of consanguineous marriages in the country, leading to increased incidences of birth defects.

Even as chromosomal aneuploidies are increasing, there are very few centres that offer quality services for premarital or prenatal genetic screening / testing and counselling. While NIPS may soon become popular in cities in India, the penetration of rural areas will be a huge hurdle as even basic medical services are yet to be made ubiquitous there.

One of the important mechanisms that can help in reaching out are referrals to non-governmental clinics and centres.

Furthermore, many rural and peri-urban patients refuse screenings or procedures due to socio-cultural and religious reasons related to the sanctity of pregnancy. There is an urgent need for bringing awareness among all sections of the society about

available and as that is fine, the baby should be ok,’’ beams Dr Kaul. The scenario has changed completely, now.

“There are so many tests available, so naturally there is confusion in the market,’’says Dr Sheetal Sharda, Consultant Clinical Geneticist, MedGenome.

The bigger challenge, as far as the genetic tests are concerned in India, avers Dr Sharda, is the lack of awareness about which tests are already available in the country.

To address this issue, MedGenome has developed certain modules to help doctors choose the most appropriate test,

the value of science when adopted in correct ways. This also means that companies and the government must invest outside sequencing technologies and personnel training.

Translating scientific knowledge Improving the molecular or genetic

quotient will determine the future progress of humanity. Both commercial and not-for-profit organizations must come forward with unique models of translating scientific knowledge to the layman. We all know that science is the basis of the modern medical practices and progress that can truly reduce the disease burden. The majority of scientists work in their laboratories and publish in scientific journals which are not suitable for general public consumption.

However, scientists always want to translate their knowledge for public benefit. Presently there are no platforms for this purpose, which opens up great opportunities. It is the right time for clinicians and scientists to join hands in grabbing these opportunities and creating platforms to translate molecular and clinical knowledge outcomes to the public. This can truly help devise an ethical way of bringing change in the society and in transmitting the true value of technological development.

The ethical discussion also brings up the question of pricing and affordability.

Even if prices are reduced, NIPS will still be a financial burden among lessadvantaged populations. They may, in spite of having knowledge of genetics. give religious or other reasons for not availing the services. A novel mechanism of subsidy for economically weaker sections may see a surge in the usage of the technology and give better value addition to scientific discoveries.

Giving birth to a baby with genetic abnormalities is often seen as a huge burden by families in the absence of a support system for the parents and the children. This can become a major cause of concern when

there are an increased number of women seeking abortions, and in places where such abortions are illegal, they end up receiving unsafe abortions.

These aspects need to be understood thoroughly before taking NIPS services ahead in the future.

The majority of NIPS offered in low- and middle-income countries, including India and China, are based on European or US accreditations. The genetic screening does not generally come under local regulatory oversight.

The legal provisions in India, which tend to focus on abortion and reproductive technologies, must also consider the value of giving proper prenatal detection of foetal aneuploidy. This gives time to families to be prepared for the birth, and have all the required resources to deal with the complications, including the social, moral and psychological consequences. The legal provisions on abortions can vary, including the regulation on foetal sex determination imposed in India to prevent sex selection.

As India prohibits sex selection, screening companies, medical practitioners and genetic counsellors must be careful to follow the applicable norms. Ultimately, the success of any genetic screening will depend on the inclusiveness of clinicians, scientists, professionals of other fields, the public, patients, insurance providers and local governments.

The author is Full-Time Director at SciGenome Research Foundation, Bengaluru

as they often put forward their queries based on patient observation and suspected indications.

If there is a differential diagnosis, the scientists in the company can identify the main etiology or the main genetic components that cause a particular kind of disorder and suggest the right kind of tests for the patients instantly.

There could be a number of variations or large chromosomal abnormalities.

Quite often, Dr Sharda continues, MedGenome gets requests for spinal muscular atrophy screening after sending OCTOBER 2018 / FUTURE MEDICINE / 21

the sample for exome sequencing. Since this disorder is a common case of exome 7 and 8 gene deletions, it can be initially tested in a PCR based small lab. If found positive for the said gene deletions, the samples can be sent to an academic lab for confirmation. “But, later, if they come to know that there are other genes such as SMN2, which is a pseudogene, also involved and that such information is important for the prognosis and to know the phenotype, then the sample needs to be tested with an MLPA (Multiple Ligation-Dependent Probe Amplification) test, where we get the ratio of how many genes are deleted and how many are duplicated. This is important for the correct prognosis.” This approach helps the patient to actually save cost by avoiding unnecessary tests or methods.

Obviously, a large section of the obstetricians in India is lacking the latest advances in the field. This is partly because genomics is, comparatively, a new discipline. It is yet to be made part of the medical curriculum. The super-specialty DM curriculum has already incorporated genetic studies and the methods quite elaborately. But the graduation level courses are yet to get updated with this emerging, but crucial area of medicine. Nevertheless, we are moving fast into the era of personalised medicine, potentially the most accurate disease detection and treatment management approach. Here again,

MARKET SHARE OF INDICATIONS SCREENED UNDER NIPT PANELS 2017-2027

genetic tests play the most critical role, she comments.

Educating care pathways

Obstetrical healthcare providers will need to incorporate more education into their care pathways.

Kimberly Martin, M.D. Senior Global Medical Director, Women’s Health Natera Inc

56% 44%

24%

Driven by increasing awareness and adoption, the global NIPT market is anticipated to grow at an annualized rate of 15% between 2017 and 2027

2027

CHROMOSOMAL ABNORMALITIES

22 / FUTURE MEDICINE / OCTOBER 2018

28% 22% 14%

2017

SOURCE: www.rootsanalysis.com

In fact, clinicians have a more active role to play in helping pregnant women with meaningful options of reproductive choice in a milieu of overwhelming genomic information.

“Obstetrical healthcare providers will need to incorporate more education into their care pathways,’’says Kimberly Martin, M.D., Senior Global Medical Director, Women’s Health at Natera Inc, a leading global player in cell-free DNA testing based in San Carlos, California.

Delving into its practicality, Dr Martin observes that it is unlikely that this can be achieved using the traditional faceto-face encounters alone. There are many opportunities for “tech” based learning that are currently available and/ or in development, including web-based videos, apps for phone/computer and even telemedicine with online genetic counsellors.

Constrained by time, providers are now receiving assistance from both the industry and professional societies to meet the growing educational needs. “This should translate into them having time to actually counsel regarding the decision making about testing, which is consonant with the goals and values of the family,’’ she recommends.

Counselling is the most important aspect

Trisomy 21 (Down syndrome) Trisomy 18 (Edward syndrome) Trisomy 13 (Patau syndrome)

2017

2027

SEX CHROMOSOMAL ABNORMALITIES Turner syndrome Klinefelter syndrome Triple X syndrome Jacob syndrome

2017

2027

MICRODELETION SYNDROMES

Cri-du-chat syndrome DiGeorge syndrome Prader-Willi syndrome Monosomy 1p36 Wolf-Hirschhorn syndrome

of NIPT, underscore all the guidelines. The objective of any prenatal screening activity should be made explicit. In a country like India, where the awareness level is rather low and familial, social and ethical considerations galore, this poses an additional challenge.

“Doctors, of course, are very open, but we have been confronted by situations where the parents hide the fact that their daughter is a carrier as it may affect her likelihood of marriage,’’says Dr Kaul. This sort of issue can present a significant challenge while implementing routine prenatal screening to detect hemoglobinopathies as proposed by India.

All this points to the necessity of social change and the need to impart the correct knowledge of such conditions amongst the public, she adds.

The awareness level, however, has gone up considerably since 2011, when NIPT was introduced, according to Dr Kadam. A lot of awareness programmes and direct education workshops among the doctors and diagnostics players were conducted. Of course, awareness about technology has been growing all over the world as well.It supported a positive response in the Indian market along with exposure to new technologies. The level of awareness among the parents and pregnant women is also high nowadays. “In fact, we and our hospital partners have started getting direct inquiries from pregnant women asking about the availability of NIPT tests,’’ says Dr Sharda.

“But still, I would emphasise the need for more coordinated efforts from the industry, the government and the medical community to maximise the utility of such technology breakthroughs in India,” she adds.

Some clinicians too seem to corroborate the view that the awareness among the public is growing pretty fast. “Many patients now come asking for the test (NIPT). Sometimes they insist on doing it,’’says Dr Ajay Kumar, Additional Professor, Department of Obstetrics & Gyenaecology, Government Medical College, Kottayam.

Most of the time, patients come well-prepared and are thoroughly informed about genetic tests.

NIPT TARGETING SNPS

Higher costs: Impeding factor?

Another big barrier that comes in the way is the exorbitant cost of genetic tests. Advances in NIPT is better, from the provider standpoint, because they can give answers to more conditions now. However, for the patient, the costs are getting enormous. In the earlier days, a karyotyping was good enough and that did not cost much. But now a prenatal microarray as the first-line test itself is hugely expensive compared with earlier tests. And if the test proves non-informative, then going into the option of sequencing increases the cost manyfold, says Dr Kaul.

Many clinicians are yet to adopt the screening test as part of their routine practice, though they are aware of NIPT. “We don’t generally ask patients to do NIPT unless we find a higher risk in an anomaly scan or the patient is

We have started getting direct inquiries from pregnant women asking about the availability of NIPT tests.

Dr Sheetal Sharda Consultant Clinical Geneticist, MedGenome

Single nucleotide polymorphisms or SNPs are small differences in the genetic code that do not cause disease but allow the creation of a unique DNA fingerprint for every individual.

These same differences can now be used to tell if twins are identical (monozygotic) or fraternal (dizygotic). Identical twins have essentially identical DNA fingerprints.

Dizygotic or fraternal twins share some of the same DNA but also have differences, just like siblings.

NIPTs use SNPs to evaluate the 1 percent of DNA that makes patients genetically different from one another.

Natera’s Panorama is the only commercially available NIPT that specifically analyzes SNPs to determine chromosome copy number, according to the US diagnostics firm. Validated at foetal fraction as low as 2.8%, this approach sequences cell-free DNA from maternal plasma to infer the foetal genotype.

The ability to differentiate between maternal and foetal placental DNA also enables SNP-based tests to identify the presence of a vanishing twin and to minimize false positives due to maternal abnormalities. It also able to pinpoint triploidy and complete molar pregnancies. The company’s validation data have shown a combined sensitivity of >99% and specificity of >99 for its NIPT. Panorama targets 13,392 SNPs, covering chromosomes 21, 18, 13, X, and Y; additional sets of SNPs are targeted for identification of microdeletions. A patented algorithm is then used to determine the chance for foetal chromosome abnormalities and foetal sex (when requested), says Natera.

OCTOBER 2018 / FUTURE MEDICINE / 23

slug

“Many doctors still cling on to the old concept that genetic diseases have no treatment”

D

r IC Verma, Professor and Senior Consultant Adviser, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, who is known as the father of human genetics in India, talks about the critical nature of the country’s genetic disease burden in an interview with C H Unnikrishnan. Edited excerpts:

How advanced is India, as a country, as far as genetic screening and testing technologies and its access are concerned?

Much effort and expense go into screening pregnant women for chromosomal disease, which affects almost 1 in 200 births. The commonest of chromosomal disorders is Down syndrome, in which there is an extra chromosome 21. Its incidence is about 1

in 800 births, but the incidence is higher if the mother’s age is more advanced, especially after 38 years. Some doctors feel that it is only the older women who should be screened for Down syndrome in their baby. However, the majority of Down syndrome babies are born to young mothers. So every woman deserves to be offered screening for Down syndrome.

Most of the genetic screening and testing technologies are available in India. However, some of the tests are expensive for the general population, and need to be subsidized by the government.

How familiar are Indian doctors with these technologies, as genetic services are still not fully integrated into the existing medical education

afraid of invasive procedures. This is because the cost of the test is too high. Most of the patients can’t afford it,’’ says an obstetrician practising in KIMS Hospital, Thiruvananthapuram, preferring anonymity.

Apprehension about the cost remains the key factor that makes many refrain from genetic tests. As a matter of fact, the availability of a large number of tests which help pick up a variety of genetic disorders has helped costs to come down drastically in the last few years, bringing the tests within the affordable range of the majority of patients, notes Dr Kadam.

Yet, many women throughout the world do not have access to such tests because of a lack of funds, either the result of restrictive terms and conditions of their health insurance or due to a total lack of coverage for such procedures. Often, these women do not have the financial resources required to pay for these tests out of pocket, observes Dr Martin of Natera.

Tech know-how vis-a-vis clinical ability NIPT, as mentioned, is recommended only as a screening test and not as a diagnostic procedure, despite the huge potential of the technology. The ability of cfDNA analysis to detect autosomal aneuploidies is far superior to any other available tests and the results are nearly comparable with 24 / FUTURE MEDICINE / OCTOBER 2018

and services?

Many doctors are ill informed about genetic screening and testing. They still harbour the old concept that genetic diseases have no treatment. Therefore, they often feel that there is no need to do genetic testing to make a precise diagnosis. Most doctors and patients in rural areas are not aware that many of the genetic disorders can be treated,.

Do you think there is an urgent need of establishing medical genetics as an additional department in medical education?

Doctors who regularly read medical journals to update their knowledge realise the importance of genetics in everyday practice. Even the standard medical books are loaded with information about genetics as applied to various diseases.

India has already started feeling the tremendous scarcity of medical geneticists and genetic counsellors.

Only a handful of institutions are providing training in medical genetics (Sanjay Gandhi Postgraduate Institute

those of invasive analysis such as amniocentesis or CVS. Nonetheless, the results of NIPT must be confirmed through an invasive diagnosis before considering medical termination of pregnancy, mandate the guidelines. This is because NIPT is less than fully accurate.

The failure, however, to touch 100% mark is purely technical. Most of the current NIPTs employ whole genome massive parallel sequencing (MPS) technology and use counting of cfDNA fragments to detect autosomal aneuploidies. The DNA sequenced comprise DNA of both maternal and placental origin. So, factors other than aneuploid foetal karyotype. including placental mosaicism, vanishing twin, maternal tumour etc., could inevitably signal false positives, studies say.

To tide over this problem and minimise false positives, some commercial companies use another approach based on single nucleotide polymorphisms.

Targeted sequencing that maps only the chromosome region of interest is yet another technology approach to NIPT. Though these tests can give more accurate results, only diagnostic techniques like amniocentesis or CVS can say with 100% accuracy whether the DNA has a chromosomal abnormality. No irreversible decisions should be made based upon a high-risk NIPT result in isolation.

HEARING LOSS MEDGONOME OFFERS GENETIC TESTING FOR COUPLES

in Lucknow, All India Institute of Medical Sciences in Delhi, Postgraduate Institute in Chandigarh, Manipal University in Mangalore). The total medical geneticists in the country may be about 100, which is totally inadequate for a country the size of India.

Similarly, these tests only measure the probability for a limited number of conditions, while amniocentesis and CVS can be used to test for a much broader number of genetic abnormalities, emphasises Nateram, which makes SNP-based Panorama NIPT. Clearly, the technical ability to test for a condition does not necessarily correspond with a clinical benefit.

Hence it is important for the companies to be certain about the benefit of every new addition.

“Test results must aid clinical decision-making and should be beneficial to patients. Each condition added to a screening panel adds to the overall false positive rate of the test and decreases the positive predictive value,’’ says Dr Schmid of Roche Sequencing Solutions, which recently included 22q11.2 microdeletion testing as part of its prenatal test portfolio. Therefore, additional cfDNA test menu options must focus on clinically relevant conditions and require comprehensive validation studies to demonstrate clinical utility in the population to be tested.

Furthermore, counselling becomes more challenging with an increase in the complexity of testing options and the potential of identifying conditions with an uncertain prognosis, according to Dr Schmid.

Test results must aid clinical decision-making and should be beneficial to patients. Each condition added to a screening panel adds to the overall false positive rate of the test and decreases the positive predictive value.

Maximilian Schmid M.D.

Head of Medical Affairs, Roche Sequencing Solutions, California

MedGenome Labs, a genomicsbased research and diagnostics company, offers genetic testing for couples with a family history of hearing loss.

Awareness and early detection are the only ways to prevent genetic hearing loss disorders from being passed down to next generations.

Couples should undergo pre-conception counselling with a genetic counsellor, especially when there is positive family history for a disorder. Such counselling sessions help the couple better understand the risk to the child as well as help recommend a suitable prenatal genetic test, according to Dr Sunitha Tella, head, Clinical Genetics and Fetal Medicine Department, Institute of Genetics and Hospital for Genetic Diseases, Hyderabad.

“In one such case, the first born child had cognitive disorders. It was recommended, to understand if the hearing impairment was due to genetic factors basis, which appropriate screening measures could be taken when they plan a second child,” she said. Dr Tella suggested the family to undergo genetic testing at MedGenome Labs, Bengaluru.

The blood samples of the parents and their first child revealed their first born had two mutations or variants in the GJB2 gene, which is associated with hearing loss, while the parents were found to be carrying one mutation each, making them ‘carriers’ of the disease. This meant that their child may have 25 per cent chance of being affected with hearing impairment.

The foetus was tested for these two variants and was found that it was only harbouring one of the two mutations found in the first child. In this case the child would be a carrier of the disease and wouldn’t suffer from hearing loss, she added.

2018 / FUTURE MEDICINE / 25

cover story

INDIA’S HIGH GENETIC DISEASE BURDEN Thalassaemia screening could open floodgates for similar tests JEETHA D’SILVA

I

n August this year, India’s health ministry proposed mandatory genetic screening of all pregnant women for thalassemia and sickle cell anaemia. Thalassemia is a significant health challenge in India with about 10,000 to 15,000 babies with β-thalassemia major born each year. One of the key points of the draft policy is government’s effort to reduce the birth of affected children through carrier screening and prenatal diagnosis.

If implemented, it will be the first instance of genetic testing becoming widely used in India and could open the floodgates for similar tests. The potential is immense.

For instance, there are almost 3.6 to 3.9 crore carriers of β-thalassemia in India, and for sickle cell disease there are about 25,00,000 carriers of the gene (Hemoglobin AS) and about 1, 25,000 patients of sickle cell disease.

In addition, India is reported to have one of the highest incidence of genetic disorders and birth defects. It is estimated that birth defect pervasiveness is 64.4 over 1,000 live births in the country, with 1 out of every 20 newborns admitted to the hospital carrying a genetic disease that eventually accounts for nearly 1 out of 10 infant mortality, indicating that India has a significant burden of neonates with genetic disorders. Globally, the prevalence of genetic conditions varies depending on the use of preventive strategies, access to prenatal screening, diagnosis and the option to terminate a pregnancy in case of severe birth defects.

Genetic testing is a relatively new science that involves the analysis of genes or genetic components, such as the DNA, RNA, chromosomes, proteins and certain metabolites, of the human body to detect variations that could cause disorders or inheritable disease.

“Genetic testing is used quite extensively these days. It has applications in every field of medicine as many diseases have a genetic component,” said Dr. I. C. Verma, senior consultant, Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi.

26 / FUTURE MEDICINE / OCTOBER 2018

DISORDERS &CHALLENGES About 10,000 to 15,000 babies with β-thalassemia major born each year.Birth defect

pervasiveness is 64.4 over 1,000 live births

CARRIERS β-THALASSEMIA

SICKLE CELL ANAEMIA

3.6 -3.9 25,00,000 CRORE

LAKHS

Jayesh Sheth, chairman of Ahmedabad based Institute of There are different kinds of genetic testing including Human Genetics. “However, there should not be indiscriminate newborn screening, in which neonates are tested for treatable use of genetic testing. Instead, it is advisable to go for a tiered genetic disorders; diagnostic testing, which is used to approach – the first test should ideally be a karyotype test, identify a specific monogenic genetic disorder, such as, Down then array complete genetic hybridisation and lastly exom syndrome or Trisomy 18. studies,” Dr Sheth said. This could ensure that the cost burden Genetic testing is also used for carrier testing, which is to the patient is minimised. used to identify people who carry one copy of a mutation Dr Sheth also recommended the that, when present in two copies, setting up of regional and nodal centres can cause a genetic disorder, such as for genetic testing. These should ideally thalassemia and sickle cell disease, be set up in government hospitals so that and predictive testing that is used to THERE SHOULD NOT BE the reach of genetic tests is greater and detect genetic mutations associated with INDISCRIMINATE USE that the cost is also reduced. Currently, disorders that appear later in life. These OF GENETIC TESTING. though there are many centres for such tests can identify mutations that increase INSTEAD, IT IS ADVISABLE tests, their distribution is largely in the a person’s risk of developing disorders urban setting and the semi-urban and with a genetic basis, such as certain TO GO FOR A TIERED rural areas have limited or no access. types of cancer.

APPROACH In the event of the government making In the West, genetic testing has pre-natal testing mandatory, the mushroomed into an industry with implementation of the same could prove centres offering at home diagnostic kits to be a logistical nightmare. that can create a risk profile for disease ranging from cancer Dr Divya Agarwal, a New Delhi based geneticist, stated that to cardiac disease and almost everything in between. in a country like ours, it may not be economically possible.

This could potentially help patients pre-empt the disease.

In addition, doctors feel that the government could do “Once you identify genetic disposition, it is possible to create well by recommending simpler screening tests rather than tailor made treatments for these diseases,” Dr Verma said. genetic testing. “Carrier screening for beta thalassemia could In India, too, there is a growing awareness about genetic be done by haemoglobin electrophoresis ,” said Dr Sheth. And testing. An internet search leads to numerous outfits within they also advocated focusing on other preventive measures India that offer to mail kits that one can send saliva samples to minimise birth defects, such as encouraging fortification to and get a detailed genetic profile. of food with essential vitamins like folic acid, which has been “More and more people are going in for genetic testing found to reduce the incidence of spina bifida. and facilities are widely available in bigger cities,” said Dr OCTOBER 2018 / FUTURE MEDICINE / 27

diagnositcs

LOST IN TRANSLATION Microdeletion syndrome is one of a frequently unsuspected group of disorders in prenatal evaluation DR PRIYA KADAM

T

hirty nine-year-old Juhi was cautiously delighted when she learned she was pregnant again.

She had previously miscarried a foetus affected with Down Syndrome. During her current pregnancy, she consulted a geneticist who suggested a test for Down Syndrome and a group of disorders called microdeletion syndromes. She opted for the test as it was non-invasive and accurate. Sadly, this time, the foetus was diagnosed with another disorder - 22q11.2 microdeletion syndrome. Though devastated, Juhi appreciated the information she received early in pregnancy, and accordingly made an informed decision.

Such information is vital to expectant parents for thought-through early pregnancy decisions and to avoid the distress caused by the birth of an abnormal baby unexpectedly.

Down Syndrome, with an incidence rate of 1 in 800 pregnancies, is the most common genetic/chromosomal disorder and is reasonably known to both the medical fraternity and the general public. From the 1960s, there have been continuously improving approaches to screen for and diagnose this and a few other significant conditions during pregnancy, given the seriousness of these conditions. However, there is another group of clinically relevant disorders caused by the deletion (loss) of a small part of a chromosome, called microdeletion syndromes. This chromosomal loss occurs very early during development and is irreversible.

Microdeletion syndromes are clinically important as they are associated with intellectual impairment, learning difficulties, autism and a host of other abnormalities, including those related to

28 / FUTURE MEDICINE / OCTOBER 2018

the heart and the kidneys. The reported incidence of microdeletion syndromes is 1 in 1000 pregnancies. These conditions are not easy to detect during pregnancy.

They were also previously considered rare and therefore not high-priority candidates for screening programmes.

Most individuals were/are identified after birth, during childhood or even during adulthood.

Unravelling DiGeorge Initially, microdeletion syndromes were described when patients with a cluster of specific features (phenotype) were observed together.

The genetic basis of these conditions began to be identified around 30

CAUSED BY A DELETION IN A SMALL AND VARIABLE PART OF CHROMOSOME 22, 22Q11.2 DELETION SYNDROME HAS AN INCIDENCE OF 1 IN EVERY 2000 BIRTHS.

years ago, with the development of techniques such as fluorescent in situ hybridization. With the development of other advanced techniques such as chromosomal microarrays, more and more areas of such repeated and specific chromosomal losses began to be identified, which correlated clinically observed syndromes.

22q11.2 deletion syndrome is commonly known as DiGeorge syndrome. Velocardiofacial syndrome and conotruncal anomaly face syndrome are the most commonly

used names for the microdeletion syndrome. It is the second biggest cause of congenital heart disease and developmental delays. Caused by a deletion in a small and variable part of chromosome 22, it has an incidence of 1 in every 2000 births. The syndrome is associated with heart defects, cleft palate, developmental delay, mental and psychiatric disorders, endocrine disorders, distinct facial features and low calcium levels among other features. The condition is associated with premature mortality, based on the severity of individual features. There is no cure and the best management strategy is a multidisciplinary approach aimed at handling individual symptoms.

Early management of symptoms greatly improves outcome. Most of the cases occur spontaneously without family history, while in 5-10% of the cases, it is inherited with 50% risk of transmitting the disorder. This risk of carrying an affected pregnancy with microdeletion syndrome is not related to maternal age and the risk remains the same throughout a womenâ&#x20AC;&#x2122;s reproductive period.

The syndrome was clinically described in English language in 1960s in children who presented with the triad of immunodeficiency, hypoparathyroidism and congenital heart disease. However, there is a huge variability in the presentation and the age of recognition of symptoms. Though common, the lack of awareness of the condition and/or testing methods and the huge variability in presentation delay diagnosis. The typical age of molecular diagnosis is around five years after numerous visits to different clinical specialties. Early identification and management is useful to improve the quality of life. Though the condition can be suspected during pregnancy

by ultrasonography if certain structural defects and cardiac anomalies are seen, there is no regular screening programme. Some cases may not have signs that can be picked up on an ultrasound.

Cell-free DNA screening Over the past two to three decades, tests for clear molecular diagnosis have been available. In the past four years, some of these conditions could be screened non-invasively by a new test that examines the cell-free DNA from maternal blood. Non- Invasive pre-natal test (NIPT) is a good screening test for the expectant parents, cost permitting.

NIPT, a simple, non-invasive DNA test, involves taking a small amount of blood from the motherâ&#x20AC;&#x2122;s arm to test for chromosomal abnormalities in the developing foetus. Screening during

INVASIVE TESTS, SUCH AS CHORIONIC VILLUS SAMPLING AND AMNIOCENTESIS POSE A SMALL BUT SIGNIFICANT RISK OF MISCARRIAGE. pregnancy can help empower the expectant parents to be more aware of the condition and accordingly seek medical help.

Other diagnostic tests for microdeletion syndromes include Fluorescent in situ Hybridisation, Multiplex Ligation-dependent Probe Amplification, Quantitative Polymerase Chain Reaction and Chromosomal Microarrays. However, these tests are

performed on actual foetal tissue obtained by invasive tests, such as chorionic villus sampling and amniocentesis. They pose a small but significant risk of miscarriage.

Microdeletion syndromes are a group of frequently unsuspected and overlooked disorders at pregnancy evaluation. Greater awareness among clinical fraternity as well as general public and the development of a routine screening programme would serve the population well in identifying these disorders early.

The author is Programme Director- NIPT, MedGenome, India

OCTOBER 2018 / FUTURE MEDICINE / 29

column

the catalyst

Revisiting primary care The success of Ayushman Bharat programme will depend on the effective transformation of point-of-care capabilities

T

MURALIDHARAN NAIR

he Alma Ata declaration of 1978, one of the most significant milestones in the field of public health, identified effective primary care as the very bedrock of a health system that aims for universal healthcare. The declaration defined primary health care as follows: “Primary health care is essential health care based on practical, scientifically sound and socially acceptable methods and technology, made universally accessible to individuals and families in the community through their full participation and at a cost that the community and the country can afford to maintain at every stage of their development in the spirit of self-reliance and self-determination.”

While there cannot be a debate on the wisdom behind the tenets of the declaration, it is evident from the state of healthcare the world over -- developed and developing included -- that the spirit of the declaration was not pursued. Instead, a hospital-centric model gained prominence, resulting in a universal challenge of a growing disease burden, a widening gap in access to care and the unsustainable cost of healthcare. However, there has been a call from the WHO in recent times to revisit the declaration and make it a reference point while designing the health systems of the future.

The state of primary health care in India, particularly in rural areas, where 70 percent of our population lives, is pathetic, as evidenced by the statistics below.

30 / FUTURE MEDICINE / OCTOBER 2018

In such a scenario, it is very welcome to see the emphasis placed on primary care through 1.5 lakhs HWC (health and wellness centre) as a critical element of Ayushman Bharat, the incumbent government’s flagship programme for reforming Indian healthcare. However, the success of this endeavour will depend on the effective transformation of point-of-care capabilities: INVESTMENT: While 1.5 lakh HWCs is an adequate number for the effective coverage of population, there is no clarity on the timeline by which these will become operational, and also on the investment needed. One estimate available on the government website puts an amount of Rs 10 lakhs and Rs 7 lakhs as one-time and recurring expenditure for enhancing an SC to HWC, which translates to approximately 15,000 cr and 10,000 cr of one time and recurring expenditure. Where is the provision for this amount, as the current provisions being discussed are not enough even for the hospital care part of NHPS? TRAINING: The effective manning of this mega initiative will need innovative thinking to increase the supply of required human resource and the government has rightly planned to upskill nurses and Ayurveda doctors to man the SCs. With the expansion of focus to include mental health, non-communicable diseases and rehabilitative care and to leverage

6

DISORDERS & CHALLENGES

Mean number of providers with degree by State

MBBS Degree Other Degrees

5

No Degrees

4 3

technology, even the traditional clinical staff at the PHC level will need substantial upgradation of their skills. Hence, it is imperative that effective resourcing on such a large scale will necessitate massive training capability for creating and sustaining the operations. It will be necessary to not delegate this critical function to the states. Instead, it should be tightly controlled by a central governing body for training and certification to ensure consistent quality.

TECHNOLOGY: Effective use of technology for both enhancing point-of-care capabilities and bridging access to specialist advice when needed through telehealth applications will be critical.

Use of artificial intelligence (AI) based applications to aid the primary caregiver can democratise clinical knowledge (applications for such use are being tested in the UK and other countries) and revolutionise the effectiveness of care at the last mile.

Culture of cost containment: We have a very large underprivileged population and the budgets will never be enough. Hence, being efficient will be a moral need. This will necessitate laser-like focus on cost containment, complete with a dedicated organisation and a holistic approach, including infrastructure design, process flow, choice of formulary (e.g.: standardise centrally, maximise use of quality generics),

Ra

Ke W ra es l tB a en Ka gal rn at ak a An dh Pun ja ra b Pr ad e Ta sh m il Na du Gu ja ra t A ss Utt a ar m Pr ad es h

0

Bi ha r ja st ha n Od i sh Ch a att isg ar Ha h ry M an ah a Hi ar m a ac ha sht ra M ad l Pr hy ad e a Pr sh ad es h Jh ar ka Utt nd ar an ch al

2

SOURCE: Quality and Accountability in Health: Audit Evidence from Primary Care Providers, J Das, et al

USE OF ARTIFICIAL INTELLIGENCE BASED APPLICATIONS TO AID THE PRIMARY CAREGIVER CAN DEMOCRATISE CLINICAL KNOWLEDGE.

choice of technology (e.g.: maximise frugal technology in diagnostics), contracting (e.g.: maximise central purchases for leveraging the economies of scale) productivity norms, a performance criteria underpinned by a robust measurement and a reporting framework to facilitate timely and effective action EFFECTIVE SUPPLY CHAIN: Public health facilities have been notorious for unavailability of medicines and related provisions. which can seriously hamper the outcome expectation from primary care. Hence it is imperative to have an agile supply chain management to ensure near 100 percent availability even while optimising the burden of inventories..

The author has long-standing association with EY India but the views are strictly personal.

OCTOBER 2018 / FUTURE MEDICINE / 31

drug approvals with locally advanced or metastatic NSCLC whose tumours express PD-L1.

Pembrolizumab in combo with pemetrexed

Lumoxiti to treat hairy cell leukaemia

T

he European Commission has approved pembrolizumab (Keytruda), Merck's anti-PD-1 therapy, in combination with pemetrexed (Alimta) and platinum chemotherapy for the firstline treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC) in adults whose tumours have no EGFR or ALK positive mutations.

This approval, the first in Europe for an anti-PD-1 therapy in combination with chemotherapy, is based on data from the pivotal Phase 3 KEYNOTE-189 trial in patients with metastatic nonsquamous NSCLC regardless of PD-L1 tumour expression status.

The data demonstrated a significant survival benefit for the combination of Keytruda with chemotherapy as compared with standardof-care chemotherapy alone – reducing the risk of death in these patients by half, the company said.

The approval allows marketing of the Keytruda combination in all 28 EU member states plus Iceland, Lichtenstein and Norway,

T

Cassipa sublingual film for opioid dependence T he US FDA granted approval to Teva to market Cassipa (buprenorphine and naloxone) sublingual film for the maintenance treatment of opioid dependence.

"We’ve taken a number of steps to advance the development of new FDAapproved treatments for opioid dependence and encourage health care professionals to ensure patients are offered an adequate chance to benefit from these therapies," said FDA Commissioner Scott Gottlieb, M.D. Opioid use disorder should be viewed similarly to any other chronic condition that is treated with medication, he added.

Medication-assisted treatment (MAT) is a comprehensive approach that combines FDAapproved medications (currently methadone, buprenorphine, or naltrexone) with counseling

at the approved dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Keytruda is also approved in Europe as a monotherapy for the first-line treatment 32 / FUTURE MEDICINE / OCTOBER 2018

and other behavioural therapies to treat patients with opioid use disorder (OUD).

Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive.

According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for treatment of their OUD cut their risk of death from all causes in half, according to an FDA release.

In June, the FDA also approved the first generic versions of Suboxone (buprenorphine and naloxone) sublingual film in multiple strengths.

of metastatic squamous or nonsquamous NSCLC in patients whose tumours have high PD-L1 expression with no EGFR or ALK positive tumour mutations and for previously-treated patients

he US Food and Drug Administration gave its nod to Lumoxiti (moxetumomab pasudotoxtdfk) for the treatment of adult patients with relapsed or refractory hairy cell leukaemia (HCL).

Lumoxiti was approved under FDA’s Priority Review.

The approval is based on data from the phase III, singlearm, open-label ‘1053’ trial of Lumoxiti monotherapy in 80 patients who have received at least two prior therapies, including a purine nucleoside analog.

The primary endpoint of the trial was durable complete response, AstraZeneca and MedImmune said in joint press communication.

The median time to haematologic remission was 1.1 months. At data cut-off, the median duration of complete response was not yet reached after a median 16.7 months of follow-up.

Capillary leak syndrome (CLS) and haemolytic uraemic syndrome (HUS), including life-threatening cases of each, have been reported among patients treated with Lumoxiti.

In the combined safety database of 129 HCL patients treated with Lumoxiti, Grade 3 or 4 CLS occurred in 1.6% and 2% of patients, respectively.

Grade 3 or 4 HUS occurred in 3% and 0.8% of patients, respectively.

In the ‘1053’ trial of 80 patients, the most common Grade 3 or 4 adverse reactions were hypertension, febrile neutropenia, and HUS. HUS was the most common adverse reaction leading to discontinuation.

Lumoxiti, which targets CD22 transmembrane protein,

is AstraZeneca's first antibodydrug conjugate (ADC).

Merck to launch two new HIV-1 medicines

D

elstrigo and Pifeltro are cleared for sale in US to treat HIV-1 infection, Merck said.

Delstrigo is a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300

mg) and tenofovir disoproxil fumarate (TDF, 300 mg).

Pifeltro (doravirine, 100 mg) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be administered in combination with other antiretroviral medicines.

Both Delstrigo and Pifeltro are indicated for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience, and are administered orally once

daily with or without food.

Delstrigo contains a boxed warning regarding posttreatment acute exacerbation of hepatitis B infection.

The approvals are based on findings from the pivotal, randomized, multicenter, double-blind, active controlled Phase 3 trials, DRIVE-AHEAD and DRIVE-FORWARD, evaluating the efficacy and safety of Delstrigo and Pifeltro, respectively, in participants infected with HIV-1 with no antiretroviral treatment history.

Jivi cleared for hemophilia A treatment

J

ivi (BAY94-9027) has been granted approval for the routine prophylactic treatment of hemophilia A in previously treated adults and adolescents 12 years of age or older in the US. The recommended initial prophylactic regimen for Jivi is twice weekly, with the ability to dose every five days and

further individually adjust to less or more frequent dosing based on bleeding episodes, Bayer said.

The FDA also approved Jivi for on-demand treatment and the perioperative management of bleeding in the same population.

The US FDA approval is based on the results of the pivotal Phase 2/3 PROTECT VIII trial comprised of prophylactic dosing, ondemand treatment, and perioperative management in previously treated adults and adolescents 12 years of age or older with severe hemophilia A. BAY94-9027 was engineered to have an

Mepolizumab as an add-on therapy for paediatric asthma

M

epolizumab (Nucala) has been cleared for marketing by EC as an addon treatment for severe refractory eosinophilic asthma in paediatric patients aged six up to 17 years.

Mepolizumab is the first and only approved biologic therapy that targets interleukin-5 (IL-5), which plays an important role in regulating the function of eosinophils, GSK said.

Mepolizumab is the firstin-class monoclonal antibody that targets IL-5. It is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils.

Inhibiting IL-5 binding in this way reduces blood eosinophils. The drug was first

approved in 2015 for severe eosinophilic asthma, Mepolizumab has been studied in over 3,000 patients in 16 clinical trials across a number of eosinophilic

34 / FUTURE MEDICINE / OCTOBER 2018

indications and has been approved in the US, Europe and in over 20 other markets, as an add-on maintenance treatment for patients with severe eosinophilic asthma.

In the US, Japan and Canada, it is approved as add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Mepolizumab is currently being investigated for severe hypereosinophilic syndrome, nasal polyposis and COPD. This marketing authorisation is based on a partial data extrapolation approach which was agreed with the paediatrics committee (PDCO) of the EMA. With this approach, efficacy and safety data from the Phase III studies included in the mepolizumab severe asthma development programme for patients 12 and over were extrapolated to children.

extended half-life by harnessing proven PEGtechnology that delivers higher sustained levels of FVIII, which extends the bloodâ&#x20AC;&#x2122;s ability to coagulate for longer. As a site-specific PEGylated FVIII, Jivi has a half-life of 17.9 hours that delivers sustained levels in the blood.

The FDA also approved Jivi for on-demand treatment and the perioperative management of bleeding in the same population.

Eravacycline for intra-abdominal infections

T

he US FDA has granted marketing authorisation

to eravacycline (Xerava) for the treatment of complicated intra-abdominal infections (cIAI).

In clinical trials, eravacycline was welltolerated and achieved high clinical cure rates in patients with cIAI, demonstrating statistical noninferiority to two widely used comparators â&#x20AC;&#x201C; ertapenem and meropenem, according to Tetraphase Pharmaceuticals, Inc. Eravacycline is indicated for the treatment of cIAI in patients 18 years of age and older.

The antibiotic drug was investigated for the treatment of cIAI as part of IGNITE (Investigating Gram-Negative Infections

EU nod for Taf-Mek combo for adjuvant melanoma therapy

T

he EC has approved dabrafenib (Tafinlar) in combination with trametinib (Mekinist) for the adjuvant treatment of stage III patients with BRAF V600 mutation-positive melanoma after complete surgical resection.

The approval is based on results from the Phase III COMBI-AD global study, which enrolled more than 870 patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy, and who were randomized within 12 weeks of complete surgical resection.

The BRAF gene provides instructions for making a protein that helps transmit chemical signals from outside the cell to the cell's nucleus.

This protein is part of a signalling pathway known as the RAS/MAPK pathway, which controls several important cell functions.

Specifically, the RAS/ MAPK pathway regulates

Treated with Eravacycline) phase 3 programmes. In the first pivotal phase 3 trial in patients with cIAI, twice-daily intravenous (IV) eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to ertapenem and was welltolerated. In the second phase 3 clinical trial in patients with cIAI, twice-daily IV eravacycline met the primary endpoint by demonstrating statistical non-inferiority of clinical response compared to meropenem and was well-tolerated. In both trials, the drug achieved high cure rates in patients with Gramnegative pathogens, including

36 / FUTURE MEDICINE / OCTOBER 2018

the proliferation of cells, the process by which cells mature to carry out specific functions, migrations and apotheosis.

This approval is the third for Tafinlar in combination with Mekinist in Europe across a variety of tumour types identified with a high level of BRAF mutation, Novartis said.

Combination use of Tafinlar + Mekinist in patients with unresectable

resistant isolates, the drug maker said.

Lanadelumab to prevent HAE attacks

F

ollowing priority review, the US FDA has approved lanadelumab-flyo (Takhzyro) injection, for prophylaxis to

or metastatic melanoma who have a BRAF V600 mutation is approved in the US, EU, Japan, Australia, Canada and other countries.

The combination of Tafinlar + Mekinist is also approved for the treatment of metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation in the US and advanced NSCLC with a BRAF V600 mutation in the EU.

prevent attacks of hereditary angioedema (HAE) in patients 12 years of age and older, Shire plc said.

Lanadelumab is a monoclonal antibody that provides targeted inhibition of plasma kallikrein, an enzyme which is chronically uncontrolled in people with HAE, to help prevent attacks.

The recommended starting dose of lanadelumab is 300 mg every two weeks. A dosing

interval of 300 mg every four weeks is also effective and may be considered if the patient is attack free for more than six months.

The FDA approval of lanadelumab was based on data from four clinical trials, including the HELP (Hereditary Angioedema Long-term Prophylaxis) Study, the largest prevention study conducted to date in HAE, according to Shire.

In the Phase III HELP study, lanadelumab reduced the number of monthly HAE attacks an average of 87% (n=27) vs. placebo (n=41) when administered at 300 mg every two weeks and 73% (n=29) vs placebo (n=41) when administered at 300 mg every four weeks.

Lanadelumab has a halflife of approximately two weeks and is administered as one subcutaneous selfinjection every two weeks at the recommended starting dose.

Shire added lanadelumab to its HAE portfolio with the acquisition of Dyax Corp.

Oral RTK inhibitor lenvatinib to treat HCC

T

he EC has granted a marketing authorization for the oral receptor tyrosine kinase (RTK) inhibitor lenvatinib (Lenvima), as a single agent for the firstline treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy.

Lenvatinib is the first new, first-line treatment for advanced or unresectable HCC in a decade to show an overall survival treatment effect by statistical confirmation of noninferiority against standard of care, according to a joint press statement by Eisai and Merck.

Lenvatinib's approval was based on results from

REFLECT (Study 304), an open-label, phase 3 trial where the drug demonstrated a treatment effect on overall survival by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC. Lenvatinib also demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival and objective response rate.

Currently, Lenvima is marketed in Japan for the treatment of HCC and in the United States for the treatment of first-line unresectable HCC. In March 2018, Eisai and Merck entered into a strategic collaboration for the worldwide co-development and co-commercialization of Lenvima.

Loteprednol for pain following ocular surgery

T

he US FDA has approved loteprednol etabonate ophthalmic suspension 1% (Inveltys) for the treatment of post-operative inflammation and pain following ocular surgery. Inveltys is the first twice-daily (BID) ocular corticosteroid approved for this indication.

All other ocular steroids are approved for four-times-aday dosing. The use of ocular steroids post-surgery is to achieve a rapid reduction of

inflammation and to promote healing of the eye. Therefore, ensuring close adherence to the steroid regimen is a critical factor for physicians in the post-surgery care of the patient and eventual overall success of the procedure, Kala Pharmaceuticals, Inc said.

Kala has initiated a third Phase 3 clinical trial, STRIDE 3 (STRIDE - Short Term Relief In Dry Eye), evaluating KPI-121 0.25% for the temporary relief of the signs and symptoms of

dry eye disease.The company expects to report top-line results for STRIDE 3 in the fourth quarter of 2019.

Kala also plans to submit a New Drug Application (NDA) for KPI-121 0.25% during the second half of 2018. The NDA will include data from three clinical trials studying approximately 2,000 patients, including one Phase 2 trial and two Phase 3 efficacy and safety trials (STRIDE 1 and STRIDE 2), the company said.

Oxervate, first rhNGF to treat neurotrophic keratitis

T

he US FDA has approved Oxervate (cenegerminbkbj ophthalmic solution) to treat neurotrophic keratitis (NK), DompĂŠ announced.

Neurotrophic keratitis, characterised by corneal scarring and vision loss, is a rare orphan condition.

Oxervate represents the first-ever topical biologic medication approved in ophthalmology, and is the first ever application of a human NGF as drug or treatment, according to the company.

Oxervate is based on cenegermin-bkbj, a novel recombinant human nerve growth factor (rhNGF) that is structurally identical to

the nerve growth factor (NGF) protein that is made in the human body, including in the ocular tissues.

The endogenous protein supports corneal integrity though several mechanisms.

NGF acts directly on corneal epithelial cells to stimulate their growth and survival. In addition, NGF is known to bind receptors on lacrimal glands to promote tear production, which may provide the eye with lubrication and natural protection from pathogens and injury. The protein also has been shown experimentally to support corneal innervation, which is lost in neurotrophic keratitis.

OCTOBER 2018 / FUTURE MEDICINE / 37

regulatory

FDCs ON THEIR WAY OUT? India slaps ban on 328 drug combos finding no therapeutic justification for such concoctions

T

he recent ban of 328 Fixed Dose Combinations (FDC) drugs with immediate effect by the Union Health Ministry is set to cost roughly Rs 2500 crore to the pharmaceutical industry in India. The ban is likely to hit 40-60 pharmaceutical companies and around 6000 brands, according to the industry experts.

The health ministry banned manufacture, sale and distribution of 328 FDC drugs after an expert panel, which was set up by the Drugs Technical Advisory Board (DTAB) to study safety, efficacy and therapeutic justification of the drugs, recommended that there is no therapeutic justification for the ingredients contained in 328 FDCs and that these FDCs may involve risk to human beings. The list of banned FDCs include many popular drugs.

Meanwhile, the ministry has restricted manufacturing, sale and distribution of six other FDCs drugs subject to certain conditions. FDCs are drugs in combinations of two or more active ingredients in a fixed ratio in a

38 / FUTURE MEDICINE / OCTOBER 2018

single dosage.

“The industry will see an erosion of about Rs 2500 crores following the ban of the FDC drugs. There are certain companies who have majority of these products and they will be affected badly,” said Daara B. Patel, Secretary General, Indian Drug Manufacturers’ Association (IDMA). However, he added that it won’t have much impact on the pharmaceutical industry in India, which has a size of over Rs 1 lakh crore.

FDCs unsafe Welcoming the ban, All India Drug Action Network (AIDAN), an

RATIONALITY NEEDS TO BE DEMONSTRATED

BY SAFETY, EFFICACY AND THERAPEUTIC JUSTIFICATION, SAYS AIDAN

independent network of several non government organizations working to increase access and improve the rational use of essential medicine, said in a statement that none of the FDCs meet the criteria of a rational and safe FDC. The people of India have been made the consumers of unsafe medicines for too long and this is one step towards rectifying the grave situation of a pharma market brimming with innumerable irrational FDCs. “It reinforces our constant demand for approval, and use, of only rational medicines in India. Rationality needs to be demonstrated by safety, efficacy and therapeutic justification. None of the FDCs meet the criteria of a rational and safe FDC. The people of India have been made the consumers of unsafe medicines for too long and this is one step towards rectifying the grave situation of a pharma market brimming with innumerable irrational FDCs,” said AIDAN. Under section 26 A of the Drugs and Cosmetics Act 1940, the Health Ministry had banned the manufacture, sale and distribution of 344 FDCs for human use in March 2016. Later five more FDCs were added to the list. The health ministry banned these FDCs after an expert committee headed by Prof CK Kokate declared them unsafe.

However, many affected manufactures contested the ban in Supreme Court and various high courts. The ministry moved the apex court challenging a Delhi high court order that quashed the ban. AIDAN had also filed a petition in the top court against the Delhi high court order.

In December 2017, the Supreme Court had asked DTAB, the country’s top drug advisory body to review manufacture and sale of FDCs.

SWEPT BY REGULATORY WAVE The ban on 328 fixed dose combinations will lead to a loss of industry revenue amounting to

â&#x201A;¹2500cr FLOXACIN+

DICLO FENAC+ NIMES ULIDE+

CEFUROXIME + LINEZOLID+

ZINC+

CETIRIZINE+ CAFFEINE

+

LEVO

BORON+

+

XICAM+

OCTOBER 2018 / FUTURE MEDICINE / 39

slug

HIGH COURT ALLOWS DRUG MAKERS TO SELL EXISTING STOCK OF FDCS

The Delhi High Court has allowed the sale and distribution of already manufactured stock of the 328 fixed-dose combination (FDC) drugs banned by the government on September 7.

Offering an interim relief to ten pharmaceutical companies, the Court directed the firms to file an affidavit with the court indicating the ‘batches already manufactured’ by them as a measure to ensure the quality of the drugs.

The Court further ordered that no coercive action would be initiated against the manufactures, stockists as well as dealers of the banned FDC drugs, as per the court directive which allows the sale of FDC drugs for the time being. The High Court, however, directed the companies to stop all manufacturing operations with regard to the banned FDC drugs.

40 / FUTURE MEDICINE / OCTOBER 2018

Subsequent to the apex court direction, an expert panel was formed under the chairmanship of Dr. Nilima Kshirsagar, Professor, Head, Clinical Pharmacology, G. S. Medical College, KEM Hospital, to review safety, efficacy and therapeutic justification of the FDCs. The panel recommended ban of these drugs citing safety issues and lack of therapeutic justification. The board in its report concluded that there was no therapeutic justification for the ingredients in 328 FDCs and that these FDCs may involve risk to human beings. It recommended banning the manufacture, sale or distribution of the FDCs in larger public interest. But 15 out of 344 FDCs in the original list, which were claimed to be manufactured prior to September 1988, were excluded from the current as the Supreme Court had stated that the government cannot ban the 15 FDCs on the basis of DTAB report.

Tip of iceberg?

“When the ban on FDCs was notified, pharma companies in court cases questioned the locus standi and powers of the Central government to ban drugs in India. That issue has been settled decisively with the recommendations of the sub-committee led by Dr. Kshirsagar” said AIDAN in its statement.

AIDAN has also urged the government to take swift action on the 15 FDCs that were excluded from

the notification on the basis of safety and efficacy considerations. “We note however, that the FDCs under scrutiny account for approximately Rs. 2,500 crore in sales and represent only the tip of the iceberg. In our estimation, the market of unsafe, problematic FDCs in India is at least one fourth of the total pharma market valued at Rs. 1.3 trillion,” it said.

Meanwhile, another round of legal tussle is expected to ensue in the coming days with many companies approaching courts against the ban.

The Supreme Court allowed sale of Saridon, Dart, a pain killer and Piriton Expectorant, which is used for common cold, cough and other conditions, in September. The apex court’s interim order came on petitions filed by GlaxoSmithKline, Piramal Healthcare and Juggat Pharma. While Saridon is manufactured by Piramal Healthcare, Piriton is owned by GlaxoSmithKline and Dart by Juggat. The court in its interim order permitted the companies to manufacture and sell the drugs until final judgement is passed. Challenging the ban, the companies reportedly claimed that the only reason given in the notification was that FDCs had no therapeutic value. In another development, Indian pharma major Wockhardt approached Delhi High Court against the ban as its anti-inflammatory drug Ace Proxyvon. According to industry sources, more companies are expected to approach courts in future against the ban.

Clinicians say that before banning the combinations, drug authorities should ensure that the individual drugs are available in the market.

Otherwise, it could lead to the shortage of some crucial medications. “There were occasions where the ban of a particular combination drug, for example, the drugs containing codeine, was banned leading to severe shortage of this important medication,’’says Dr Vinod B Nair, an otolaryngologist from Kochi, adding that “so long as it is not going to affect the availability of the crucial medications the ban wouldn’t make much impact in day to day practice.”

column

trialomics

Harnessing AI for healthcare Artificial intelligence is unlikely to replace doctors, but is expected to optimize and improve their medical skills

“I

DR ARUN BHATT

Writer is a consultant on clinical research & development from Mumbai. arun_dbhatt@hotmail.com

believe this artificial intelligence is going to be our partner. If we misuse it, it will be a risk. If we use it right, it can be our partner.” - Masayoshi Son, Japanese business magnate.

Artificial intelligence (AI) is the name given to techniques that use software to mimic human cognition in the investigation of complex health data and information. AI is revolutionizing healthcare with its access towards a large amount of health data and rapid advances in analytical techniques. AI is considered augmented intelligence as it can help in reducing diagnostic and therapeutic errors and provide real-time interpretations for health risk signals and health outcome prediction. AI systems analyse a variety of data – clinical examination, laboratory data, diagnostic imaging, genetic testing and electrodiagnosis – to improve medical decisions.

AI devices consist of 1) machine learning (ML) techniques and 2) natural language processing (NLP) methods. ML procedures analyse structured medical data - e.g., imaging, genetic and electrophysiology, to cluster patients’ characteristics or to determine the probability of disease outcomes. NLP methods evaluate information from unstructured data - e.g., clinical case notes and medical journals to complement and enrich structured health data.

AI applications have the potential to be used in diverse health conditions. However, most of the AI research focuses on disease areas with high mortality - e.g., cancer, nervous system disease or cardiovascular disease. AI systems have been used for diagnosis of skin cancer from clinical

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images, diagnosis of cardiac disease using cardiac images, to restore the control of movements in patients with quadriplegia, early detection of Alzheimer’s disease, early stroke prediction by employing a movementdetecting device and predicting and analysing the performance of stroke treatment. AI has also been utilized to detect congenital cataract disease using ocular image data and diagnose diabetic retinopathy through retinal fundus photographs. The accuracy, specificity and sensitivity of AI diagnostic systems are high and superior to those of experienced physicians. However, AI is still in the early stages of research and adoption in medical care. Besides, its real-life implementation is facing regulatory challenges.

AI pose a new challenge for physicians, some of whom are concerned that this advanced technology will replace them. But the fears seem unfounded. AI is unlikely to replace the doctors but is expected to optimize and improve their medical skills.

Dr Abraham Verghese, a well-known author from Stanford University, opined that “the two cultures – computer and physician – must work together (JAMA Jan 2, 2018).” AI has the potential to reduce tedious administrative tasks, handle large volumes of medical data and information, and provides an opportunity to integrate the expertise of medical practitioners and intelligent automation.

AI is called the stethoscope of the 21st century, says Dr Bertalan Meskó. The techsavvy physician of the 21stcentury should not fear AI tools, but should be ready to harness benefits of augmented intelligence in her practice.

straight talk

“INDIA WILL SOON MAKE THAT BIG REVOLUTION OF CHEAPER ROBOTIC SURGERY” One of the major breakthroughs in the area of gynaecological endoscopy that the world is now waiting for is cheaper robotic surgery. And, it is shortly expected from India, a country that has already produced many innovative endoscopic devices and is also home to many of the the world’s most skilled endoscopic surgeons, says PROF. LISELOTTE METTLER, who is loved and respected as a great teacher by most of India’s well-reputed endoscopists.

Prof. Mettler,an AustrianGerman surgeon specialised in endocrinology, reproductive medicine, gynaecological endoscopyand gynaecological oncology, is a professor emeritus of the Department of Gynaecology and Obstetrics at Kiel University, Germany. Mettler, who conducted one of India’s first endoscopic surgeries at Mumbai’s Breach Candy Hospital in 1973 and has also authored more than 600 publications and several books on gynaecological endoscopy, spoke to C H UNNIKRISHNAN for Straight Talk on the sidelines of a three-day International Society for Gynaecologic Endoscopy (ISGE) conference held in Pune in September. Edited excerpts:

You have been very regular to India as many of your students successfully practice here and you have also conducted several endoscopic surgeries in Indian hospitals.

What are the key differences that you see in India and the West as far as the practice of this speciality is concerned?

There is not much of difference in both these markets as far as the technology and the skill-set of doctors are concerned.

In the field of endoscopy in particular, the technology and procedures are almost the same that Kiel Hospital -Gynaecological Endoscopy Department in the University of Kiel,introduced in the early seventies. But, Indian doctors have really put more skills into it. I would say Indian doctors are far more efficient as they manage complex surgeries here despite limited infrastructure and low affordability of patients. Since most patients in the West are insured and they don’t have to pay out of pocket, costly equipment and advanced procedures are easily affordable there. But, the situation in India is different and the doctors actually use their capabilities much more efficiently to overcome the limited resources. Many of the devices that Indian doctors use in endoscopic surgeries today are indigenous and very innovative, which have made these surgeries cheaper here.

But, does it make the surgeries poor in quality as well here as compared to the West?

Not at all. You have brilliant doctors in India, who are capable of using the limited resources for optimum utility by putting their skills in it. The country has technical as well as manufacturing talent to innovate products that suit this market in terms of cost. The other important fact that I would like to add here is that many brilliant doctors in India are also quite passionate about the work that they do and they put their hundred percent in such surgical procedures. I have seen that Indian doctors, who are well-versed with endoscopic procedures, have really modified the techniques and modalities to make it much easier for the doctor as well as the patient.

If that is the case, India can very well attract patients from even Western countries isn’t it?

Of course, there have been patients coming from the West for such surgeries. I have sent a couple of my own patients from Germany to India for gynec-oncology surgeries to a hospital in Pune, where one of my old students, who is a brilliant endoscopic surgeon, operated on them. I am sure

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OCTOBER 2018 / FUTURE MEDICINE / 45

healthcare set-ups, except a few centres of excellence, are still poor in terms of infrastructure and latest technologies, many in the private sector are comparatively much better now. Indian hospitals in general were in a very bad condition as far as infrastructure and quality standards were concerned earlier. I myself have witnessed doctors and other staff eating even in the operation theatres and throwing the bones on the floor, which is no more the case now. Indian hospitals are getting better and cleaner, though there is still scope for improvement.

What are the latest breakthroughs in endoscopic surgery?

Thoughthe basic technologies that are used in the endoscopic surgery are more or less the same today as I mentioned earlier, there have been a lot of improvisations and modifications that have taken place in the

I myself have witnessed doctors and other staff eating even in the operation theatres and throwing the bones on the floor, which is no more the case now.

there are all possibilities that patients can come from even developed countries to India as the procedures and expertise that is available are not less than any other place and there is also a significant cost difference as compared to the US and Europe. I would say that the cost here would be around one tenth of the cost that prevails in those markets.

How equipped are Indian hospitals as far as quality standards and the overall healthcare systems are concerned to cater to patients, who are used to an evolved set-up in the developed markets?

Indian hospitals are no more the same as they were in the seventies or eighties. Though the public or government 46 / FUTURE MEDICINE / OCTOBER 2018

devices and supportive systems over the last few years as medical technology is a fast evolving area. While 3D endoscopy and robotic surgeries are comparatively later breakthroughs, it is still very expensive all over the world. This is the same situation in India too, though there are only very few hospitals that have facilities for robotic surgery and 3D endoscopy here at present.

In this context, one of the most soughtafter and shortly expected breakthroughs in endoscopy is a robotic surgery developed

by India using its inherent talent in inventing cheaper and better variants of expensive products and systems. As far as I know, the efforts for developing a cheaper robotic surgery in India are at a very advanced stage currently, and once it is out in the market, it will be a big revolution across the world.

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

education

DOCTORS SUE MCI ON NEW TEQ RULES Petitioners argue that there was no age limit when they joined

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group of doctors in Tamil Nadu has filed a petition in Madras High Court challenging the maximum age limit of 40 set by the Medical Council of India (MCI) for the post of senior resident or assistant professor in medical colleges. In their petition, the doctors have requested the court to declare the amendment as unconstitutional, ultra vires, discriminatory and illegal.

The public interest litigation (PIL), which came up for hearing before the bench of Justice S. Manikumar and Justice Subramaniam Prasad, was posted for the next hearing on September 19 as the MCI sought time for filing counter affidavit.

Last year, MCI had made certain changes in Teachers Eligibility Qualifications (TEQ) rules. The changes include the maximum age limit of 40 for appointment to the post of senior resident with effect from June 8, 2017. In their affidavit, the petitioners stated that they joined for post graduate courses before the changes were effected in rules and there was no age limit when they joined. In November 2017, the state government sent a proposal to the

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central government asking it to drop the criteria of age limit as it would affect medical administration and career of the doctors who have joined for PG courses. The government has also stated that the move will prove counterproductive.

Subsequent to the notification, MCI clarified that amendments would be applicable prospectively from the date of notification and will not have any effect on appointments or promotions made before the date of notification.

Therefore, residents already working on the post of senior resident after passing DNB or Diploma Course can continue to hold the same post. It has further clarified that those who are doing post graduation after the age of 40 years will not be eligible for the post of Senior Resident and

MCI CLARIFIED THAT AMENDMENTS WOULD BE APPLICABLE PROSPECTIVELY FROM THE DATE OF NOTIFICATION.

they cannot be appointed as Assistant Professor directly after PG and promoted as Associate Professor after gaining five years of experience as assistant professor. It further clarified that if a person has done DNB from MCI recognised institute, then he or she will be considered equivalent to MD/MS to be eligible as Senior Resident. If the person had done DNB from institutes not recognised by MCI, then he or she has to do three years of Junior Residency in the concerned subject from MCI approved institute to be eligible to become SR. MCI later clarified that a candidate having MBBS and DLO (ENT) qualification has worked as JR for a period of one year in ENT after PG would require MD degree in the subject concerned. Thereafter one-year senior residency is mandatory for the post Assistant Professor in the subject concerned. It has also clarified that requirement of one year senior residency for the post of assistant professor is applicable only to those disciplines where posts of senior residents is prescribed as per the minimum standard requirement of MCI.

case reports

HOW SHE REGAINED HER LOST TASTE A new lease of life to a 70-year-old lady crippled by multiple progressive heart disorders ­—thanks to TAVR DR ANOOP AGRAWAL

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rs. Sharma (name changed) couldn’t taste her food anymore. “Just like my hair, my tastebuds are also aging,” she thought. Mrs. Sharma, at 70 years of age, had been a well-kept lady until the previous year. She had enjoyed a healthy, active lifestyle in her youth and adulthood.

With an academic bend of mind, she used to teach until her early 60s. At around 61 years of age, she was diagnosed with a bicuspid aortic valve (BAV) that had led to severe aortic stenosis (AS), and was advised to undergo surgical aortic valve replacement (SAVR).

Overwhelmed by the flow ON THE TOP OF SEVERE of information, Mrs. Sharma AS, SHE HAD DEVELOPED ended up refusing surgery SEVERE AORTIC at the time. Over the next REGURGITATION, SEVERE few years, she continued to function independently and MITRAL REGURGITATION forgot about the deformed AND SEVERE LEFT valve sitting in her heart.

VENTRICULAR SYSTOLIC Last year, she started DYSFUNCTION. noticing exertional shortness of breath upon walking a few hundred meters. Over the next few months, she slowed down her life to compensate for her exertional symptoms. Slowly, she started developing dyspnea on walking within her house. She lost interest in her food. Her sleep was interrupted with frequent episodes of breathing difficulty. By the time she touched 70, she had lost almost 9 kg over a period of six months due to early satiety and ageusia. She was restricted to her room due to her inability to walk longer distances. Lately, she also started fainting at home, only to regain her senses after a minute or two. It was so frequent that it almost became routine for her and her family. She did seek medical attention for her progressive illness and came up with unanimous feedback: “She needed SAVR, but the risk was too high.” Not ready to undergo a surgery risking her life, she decided to continue

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with medicines alone, which obviously weren’t working.

Sometime during this hustle, she was referred to me for further evaluation. What I saw was a thin, frail lady who had to take periodic pauses in between her sentences to catch her breath. Even before taking a look at her medical records, I knew that patients with that degree of cardiac cachexia rarely do well with heart surgery. Her medical records made me concerned. On the top of severe AS, she had developed severe aortic regurgitation, severe mitral regurgitation and severe left ventricular systolic dysfunction.

Essentially, the blood in her heart was flowing the wrong way. I voiced my concerns to Mrs. Sharma and her family regarding the gravity of the situation and that there wasn’t an easy way out, with or without surgery. I asked her about her goals in life. “I want to get back to shopping,” she replied without any hesitation. We discussed at length about her options, what we can do without imposing a significant procedural risk on her. We discussed about transcatheter aortic valve replacement (TAVR).

TAVR is a procedure where a bioprosthetic valve is crimped and loaded on to a catheter, inserted through groin in a minimally invasive fashion, and implanted in place of the diseased aortic valve. TAVR is approved for patients with severe AS who are considered higher risk for SAVR. We discussed Mrs. Sharma’s case with cardiothoracic surgeons for her eligibility for surgery. After the surgeons deemed her very high risk for surgery, we opted for TAVR, knowing that TAVR will only address problems related to the aortic valve. This was nonetheless her best chance.

After essential investigations, she underwent successful TAVR without any complications. The procedure was performed in the cardiac catheterization laboratory in a complete sutureless fashion. She was extubated immediately after the procedure, was able to talk and eat food that evening. The major hurdle was over and she recovered in a predictable fashion. She was transferred to the room on the third day, was discharged home on day 4. Her postprocedural events were nothing short of magical. She was

able to hold long conversations on the evening of the procedure itself. The ability to talk was a luxury to her and she wanted to talk just about anything. That night she slept lying flat on the bed without gasping for breath, something she couldnâ&#x20AC;&#x2122;t do for the past one year. Next day, she finished her entire meal for the first time in months.

On the third day, she reached out for the

television remote and watched a random show for more than 30 minutes. Her son was amazed at her behaviour as previously she would get fatigued at home just by watching television for less than 10 minutes. She climbed the stairs up one floor for the first time in more than three years. On her follow up in the out-patient clinic after a few weeks, she reported that she had gained almost 3 kg weight by virtue of being able to eat. Her taste buds were back, which added pleasure to what she was eating. And yes, she was back shopping.

TAVR is the most disruptive medical innovation that modern medicine has seen in the past decade. Life-changing outcomes, as seen in this case, are not exclusive to Mrs. Sharma. The majority of the patients with severe AS who have high surgical risk can be expected to have a similar outcome. TAVR has evolved into both a bail-out strategy in otherwise extreme surgical risk patients, as well as first-line therapy for patients with intermediate surgical risk profile.

The author is Consultant, Interventional Cardiology, CARE Hospitals, Banjara Hills, Hyderabad

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case reports

A BOON OR BANE? Prenatal diagnosis can help parents make a choice about the foetus in a manner that is more acceptable - emotionally and rationally

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renatal testing and its perceived benefits have been in focus for a long time. There has been widespread debate and passionate arguments on both sides. In India, where the law allows termination of pregnancy before 20 weeks, there are several prenatal tests that are available only after 20 weeks. This dichotomy produces considerable anxiety and stress to would-be parents who may need such information within the legal timeline for pregnancy termination.

Here is a success story in which prenatal tests were able to relieve the parents of their stress and sleepless nights.

Maya (name changed) was extremely excited at being pregnant and was looking forward to a healthy baby.

However, the 12-week routine sonography was about to WHILE THE AMBIGUITY IN change her perspective on REGULAR SONOGRAPHY the pregnancy. Ultrasound FINDING WAS THE REASON imaging identified a small dorso-lumbar swelling in the FOR MANY SLEEPLESS foetus. The doctors treating NIGHTS, AN IN-DEPTH her, in her rural town of STUDY SUCH AS THE Maharashtra, were unable to FOETAL MRI WAS ABLE provide her further guidance TO ALLEVIATE HER ANXIETY and decided to follow-up AND CONCERNS. with a sonogram. The 22week sonography confirmed the presence of the cyst, while the foetus displayed normal movement with no other abnormalities detected.

The swelling could be indicative of either a meningocele or meningomyelocele, which are common congenital defects caused perhaps due to folic acid deficiency, exposure to certain drugs such as antiepileptic valproate, or other illnesses such as diabetes. Genetic and environmental components may also be involved. In the case of Maya, the cause of the swelling was not determined.

Meningocele is a cystic swelling formed by the protrusion of the dura and arachnoid mater without the involvement of the spinal cord. Treatment is rather straightforward, involving postnatal surgical repair. By contrast, meningomyelocele is a far more serious condition where, in addition to meningeal protrusion, there is the involvement of the spinal cord.

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This results in the weakness of both lower limbs, bowel and bladder incontinence and ultimately, a wheelchair-bound life.

Hydrocephalus is another associated condition with meningomyelocele that involves the enlargement of brain cavities due to fluid accumulation, resulting in cognitive dysfunction, papilledema, optic atrophy and blindness. Though shunt placement surgery alleviates symptoms of hydrocephalus, the procedure comes with its own set of neurosurgical complications. Thus, the prognosis for a meningomyelocele is far worse compared to meningocele.

In the case of Maya, since sonography could not help in differentiating the type of lesion in the foetus, the patient was referred to Mumbai to a leading gynecologist and obstetrician, Dr. Nikhil Dattar, who further referred Maya to a paediatric neurologist, Dr. K. N. Shah, to advice on the prognosis of the foetus. A foetal MRI was done as a further diagnostic test. The MRI confirmed that there was no hydrocephalus, and the condition was diagnosed to be meningocele. Based on these results, Maya was advised to continue with the pregnancy and then consult a neurosurgeon for surgical removal of the cyst postnatally.

The foetal MRI turned out to be a boon for the patient. While the ambiguity in regular sonography finding was the reason for many sleepless nights for Maya and her family, a more robust and in-depth study such as the foetal MRI was able to alleviate her anxiety and concerns. â&#x20AC;&#x153;The parents are extremely relieved and very happy that their unborn foetus

has a good prognosis and the condition is treatable by postnatal surgery. They are tremendously thankful for the advances in prenatal testing and the closure they have received,â&#x20AC;? says Dr. Shah.

The outcome for Maya was good. However, had the foetal MRI indicated a meningomyelocele as the diagnosis, this narrative would have been entirely different. The parents would have had to undergo counselling and would need to consider aborting the foetus. Indian laws dictate that pregnancies beyond 20 weeks cannot be legally aborted.

Since the pregnancy had already run into the 23rdweek at the time of the foetal MRI, this case would have needed to be considered by the Supreme Court. In recent past, the Supreme Court has been lenient in granting permission for late abortions for mothers who request them in the light of poor prognosis for their foetus. Specially, Dr. Nikhil Dattar has been instrumental in highlighting such cases and has been successful in helping parents in their cause. Prenatal testing can be a boon not only to alleviate anxiety, but also in helping parents make a choice about the foetus in a manner that would be more mentally, emotionally and rationally acceptable.

­DR SHIVANEE SHAH

OCTOBER 2018 / FUTURE MEDICINE / 53

case reports

SLEEP-ONSET SEIZURE Here is a case of long QT syndrome which manifested as a seizure-like activity while falling asleep

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enetic testing can go a long way in determining the treatment and outcome of a disease in a patient. Here is a case of a 19-year old girl who presented with a history of seizures at the neurological department at Amrita Hospital, Kochi, but turned out to have a heart condition.

Genetic testing helped identify the exact mutations which dictated her treatment modality.

This patient had a history of seizures, where during each episode she was reported to become unresponsive with seizure-like activity while falling asleep. These episodes were short lived; during her first attack, she was only unresponsive for a brief period, and did not receive any ABOUT 75% OF THE medical attention. However, INHERITED LONG QT during her subsequent SYNDROME IS CAUSED DUE episodes, she had up-rolling TO MUTATIONS IN 3 ION of eyeballs along with unresponsiveness and was CHANNEL PROTEINS THAT brought to the hospital.

CAN RESULT IN ONE OF Brain CT was normal, and THREE TYPES OF LONG QT she was diagnosed with SYNDROME — TYPE 1, 2 OR 3. epilepsy. She was started on sodium valproate as the anti-epileptic drug, but since she also complained of a vague chest pain, she was referred to the cardiology department for a consultation. Here she underwent an ECG, which showed a prolonged QT interval of 506 milliseconds (QTc), which is markedly above-normal. The working diagnosis was that of ‘long QT syndrome’.

Long QT syndrome may occur in response to certain medications. However, in the majority of the cases, it is an inherited autosomal dominant syndrome typically caused due to a mutation in one of 17 cardiac ion channel proteins.

Symptoms include transient loss of consciousness, seizures and irregular beating of the heart which prevents circulation of blood to the brain and can result in loss of consciousness.

About 75% of the inherited long QT syndrome is caused due to mutations in 3 ion channel proteins that can result in one of three types of long QT syndrome — type 1, 2 or 3. Type 1 (LQ1) is caused due to a disruption of the potassium ion channel activity and the consequent disruption of the heart’s electrical activity. Arrhythmias in such cases are typically triggered due to physical exertion and such episodes tend to

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stop without medical intervention and are less likely to be fatal. Type 2 (LQ2) is caused due to insufficient potassium ion activity in the heart and can be triggered due to emotional stress and loud noises. While types 1 and 2 are due to mutations in potassium ion channels, type 3 (LQ3) is due to mutations in sodium ion channels and occurs due to low levels of sodium flow in the heart, leading to arrhythmia. Such episodes

are typically triggered during sleep or rest and are more likely to be fatal. Molecular testing is an important aspect of identifying the type of long QT syndrome and can help in confirming clinical diagnosis as well as in guiding treatment strategy. LQT1 and LQT2 are caused due to mutations in the potassium channel genes, KCNQ1and KCNH2, respectively, while LQT3 is caused by mutations in a sodium channel gene, SCN5A. ‘For accurate treatment modality, we recommended our patient to undergo molecular testing,’ said Dr. Hisham Ahamed, Associate Professor in Cardiology, Amrita Institute of Medical Sciences and Research, Kochi. Her family agreed, and her blood sample was sent to MedGenome Labs, Bengaluru, for a cardiac channelopathy panel. This panel can identify mutations in cardiac ion channels that may result in any abnormal variation in QT interval. The genetic panel results showed that the patient had a mutation in KCNH2and was therefore diagnosed as having type 2 long QT syndrome.

While type 1 patients show good response to using medications such as beta-blockers, type 2 patients generally do not respond as well to such treatment and are typically

advised for implantable devices such as an implantable cardioverter defibrillator (ICD), if they are considered high-risk. Until the patient’s family could agree for such a procedure, the patient was started on betablockers, since a subset of type 2 patients can benefit from such medication as well.

The beta-blocker therapy has been effective thus far for this patient. Two years later, she has experienced no further episodes and her heart rhythm has returned to normal on its own. ‘’Our patient has been fortunate that the beta-blocker treatment has worked for her, although we would like to see the patient follow through on the recommended ICD implant,” says Dr. Ahamed. ‘’The lesson learnt from this case is that ECG should be performed in young individuals with a history of seizures to rule out cardiac concerns.”

­DR SHIVANEE SHAH

OCTOBER 2018 / FUTURE MEDICINE / 55

case reports

A LONG-WINDING PATH TO SPENCDI Many a time, a definitive diagnosis is the result of a difficult trajectory

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one-year-old female child was brought to a tertiary case hospital in Mumbai with fever, pallor, and conjunctival and intracranial hemorrhage. Blood tests revealed low platelet counts and hypothyroidism.

Bone marrow aspirates indicated the presence of platelet precursors, and suggested that the platelets were being destroyed. An MRI was also done and showed multifocal hemorrhagic areas in the cerebral parenchyma and cerebellum. The patient was thought to have immune thrombocytopenic purpura (ITP) and was treated with packed RBCs, platelets, intravenous immunoglobin (IVIg), methylprednisolone and dapsone for ITP, and for

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hypothyroidism with L-thyroxine. Steroids and dapsone were tapered and stopped after 6 months along with L-thyroxin. The patient did well for a few months and then returned to the hospital at age 2 with fever, cough, cold, and thrombocytopenia. This time she was treated with antibiotic therapy, oral steroids and dapsone. The patient had a 3rd admission to the hospital at age 3 with purpura and she was started on cyclosporine syrup and discharged. This treatment regime was effective for a few years.

However, at age 4, the child was brought to Lilawati DURING DISCUSSIONS Hospital and Research Center, Mumbai, to consult WITH OTHER DOCTORS, SHE with Dr. Swati Kanakia, a REALIZED THAT PERHAPS pediatric hemato-oncologist.

HER CHOICE OF KEYWORDS The patient presented with WAS NOT CORRECT. bleeding in the skin, another intracranial hemorrhage, and low platelet count. An MRI showed calcification in the basal ganglia and evidence of the previous intracranial bleeding. Based on the history, the patient was started on IVIg for treating low platelets. Further, even though normally platelets are not given as therapy in such cases as they would be expected to be destroyed in the body, this patient was again given platelets as well because of the intracranial hemorrhage, and started with cyclosporine syrup.

In addition, Dr. Kanakia observed certain morphological abnormalities including short stature, high arched palate, low set ears, and wider wrists than normal. Wider wrists are typical signs of rickets and an X-ray of the wrist was done which indeed showed typical signs of rickets. Blood tests for vitamin D, calcium, and phosphorous however did not corroborate with the clinical findings for rickets.

This was indeed an atypical case where the patient had an early onset of ITP, was not responsive to treatment over long periods of time, had two intracranial hemorrhages, calcification of basal ganglia and showed signs of abnormal facies. In addition to these, she was strongly positive for alloantibodies against red blood cells as evidenced in a direct Coomb’s test and thyroid antibodies causing hypothyroidism. Such autoantibodies are evidence of autoimmunity. Dr. Kanakia was not satisfied with the diagnosis and treatment being offered to the patient, and continued to search for a more accurate diagnosis and better treatment options. She searched the OMiM database for other similar cases, but was not able to come up with anything similar. During discussions with other doctors, she realized that perhaps her choice of keywords

was not correct. She was including the keyword ‘rickets’ due to the wider wrists that are characteristic of rickets. However, once she replaced ‘rickets’ with ‘metaphyseal dysplasia’, she was able to find a very similar condition called spondyloenchondrodysplasia with immune dysregulation (SPENCDI).

As per the description, ‘SPENCDI is an immunoosseous dysplasia combining the typical metaphyseal and vertebral bone lesions of spondyloenchondrodysplasia (SPENCD) with immune dysfunction and neurologic involvement’ The patient’s condition seemed to fit well with the description.

SPENCDI is caused by a homozygous mutation in the APC5gene on chromosome 19p13. Genetic testing was carried out, and consistent with the clinical symptoms, the patient was found to carry a homozygous deletion in the APC gene that results in a truncated protein. The patient’s parents also underwent genetic testing, and they were found to carry the heterozygous mutations.

Based on this genetic identification, the patient had a confirmed diagnosis of SPENCDI and was accordingly continued on cyclosporine. The dosage of cyclosporine was kept at a minimum dose just to maintain the platelet levels at a safe count of 30,00040,000/uL. The patient is doing well as of now.

The genetic identification was not only important for adequate treatment and management of the patient, but would also be important in case the parents decided to have another child. Prenatal testing can be used to determine whether the child would be homozygous or heterozygous, allowing for the option to terminate the pregnancy if required. Such prenatal testing may therefore prevent another child with the same genetic disorder. Genetic testing can also be done for close family members to assess hereditary mutations.

“Accurate diagnosis gives the patient/ patient’s family a sense of closure and helps them prepare for their next child. Even in this age of technological advances, clinical judgement is extremely important. To be able to diagnose accurately, it is important to understand which tests to run,” Dr. Kanakia shares her learnings from this case.

­DR SHIVANEE SHAH OCTOBER 2018 / FUTURE MEDICINE / 57

case reports

EXON SKIPPING FOR DMD Treatment for muscle dystrophy can vary depending on the type.

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

M

uscular dystrophy is group of muscle disorders characterized by progressive muscle weakness, with Duchenne Muscular Dystrophy (DMD) being the most common. DMD is an X-linked recessive disorder primarily affecting males, with women being carriers. DMD is characterized by initial proximal muscle weakness of the pelvic girdle that eventually progresses to the shoulder girdle muscles. The onset of symptoms typically occurs between 3 to 5 years of age and by the age of 13-15 years, the child is generally wheelchair-bound. DMD is caused due to mutations in the dystrophingene which lies on the short arm of the X-chromosome (Xp21.2). The dystrophingene encodes the protein dystrophin, which plays a key role in maintaining the integrity of the cell membrane of skeletal and cardiac muscle cells. In the absence of dystrophin, muscle fibres disintegrate, resulting in the muscle weakness observed in DMD. One such nine-andDYSTROPHIN GENE IS a-half-year-old boy was ONE OF THE LARGEST brought to consult Dr. K. N. KNOWN GENES, CONSISTING Shah at Lilawati Hospital OF 79 EXONS, MANY OF and Research Centre, WHICH ARE REPEATING Mumbai. His previous history revealed that he was born SEGMENTS. to parents from a nonconsanguineous marriage and had one female sibling.

He was born via a normal, full-term pregnancy, and showed normal milestones up to 2 years of age. However, after two years, his parents noticed that his walking was delayed, though his social and cognitive milestones were normal. It was also reported that he was unable to climb stairs and his calf muscles had begun show pseudohypertrophy. As his condition slowly progressed, he was unable to get up from a sitting position without additional support to his knees, an observation that is commonly called the Gower’s sign and is classically observed in DMD children. Creatinine phosphokinase (CPK) levels, a marker of muscle injury, are consistently elevated in patients with Duchenne’s and even this child had a very high level (20,000 U/L) of CPK, strongly indicative of muscle dystrophy. However, Dr. Shah also cautions that elevated CPK levels cannot specifically confirm a diagnosis of DMD, since it is simply an indicator of muscle damage, and not indicative of DMD specifically.

58 / FUTURE MEDICINE / OCTOBER 2018

While the gold standard of diagnosis for DMD is muscle biopsy followed by immunohistochemistry or western blot for dystrophin protein, new technological advances involve diagnosis via genetic testing. To appreciate how genetic testing can help diagnose DMD, it is first important to understand the dystrophingene at the genetic level and the types of mutations that have been identified in the recent past. Dystrophin gene is one of the largest known genes, consisting of 79 exons, many of which are repeating segments. Typically, mutations in this gene are either deletions or duplications of single or multiple exons.

A deletion or duplication of an exon can result in a change wherein dystrophin cannot be expressed at all. Such a mutation is called an ‘out-of-frame’ mutation.

Alternatively, in some instances, even though some exons maybe deleted or duplicated, the protein may still be expressed, albeit one that is not as effective as the wild-type one. Such mutations are called ‘in-frame’ deletions. Thus, the type of mutation can determine quantitative as well as qualitative changes in the expression of the dystrophin protein, resulting in different disorders. For instance, if the mutation results in the deletion of an exon due to which dystrophin cannot be expressed at all, the resulting dystrophy is DMD. However, if the mutation results in an exon being deleted, despite which dystrophin can be formed, then the resulting dystrophy is a milder version called Becker muscular dystrophy or BMD. Since the progression of BMD is much slower than in DMD, and the treatment and management can vary depending on the particular muscle dystrophy, it is often critical to carry out a differential diagnosis by genetic testing.

Multiplex Ligation-Dependent Probe Amplification (MLPA) is a commonly

employed genetic detection test, which can detect up to EXON SKIPPING IS A 70% of DMD positive cases.

In the event of a negative MUTATION-SPECIFIC MLPA result, clinicians THERAPY IN WHICH A still have the option of SMALL PIECE OF DNA CAN confirming the disease using BE INTRODUCED SUCH next generation sequencing, THAT IT WILL BIND TO A which can pick up about PARTICULAR EXON. 98-99% of the positive cases. However, muscle biopsy still remains the final confirmatory test. In this case, Dr. Shah proposed that MLPA be done, and the results revealed that exon 43 was deleted, which confirmed the clinical diagnosis of DMD. Genetic counselling would be important in case the parents wish to have another child, since prenatal genetic testing via MLPA at early stages of pregnancy can help determine whether the male child would have DMD. The prenatal tests can also help parents decide whether they should terminate such a pregnancy.

Further, the parents of the boy were advised to get his sister also genetically tested to determine if she was a carrier for DMD mutation.

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

hope for the future. Several research studies have been carried out for different genetic therapy approaches. Exon skipping is a mutation-specific therapy in which a small piece of DNA can be introduced such that it will bind to a particular exon and encourage the cell to skip reading that exon, thereby effectively converting an out-of-frame mutation to an in-frame mutation. Such a therapy would allow DMD-type clinical conditions to mimic BMD-type clinical conditions, which are far more manageable and have better prognosis. However, till date, only a few specific therapies are approved. For Dr. Shahâ&#x20AC;&#x2122;s patient, there is no therapy for a deletion of exon 43. The only US FDA approved therapy is for deletions that can be corrected by skipping exon 51, involved in about 13-20% of DMD cases.

However, research is ongoing, and it is likely that other, newer exon-skipping targets become available in the future.

­DR SHIVANEE SHAH OCTOBER 2018 / FUTURE MEDICINE / 59

research snippets

Grass pollen exposure in utero shows possible risk recent study provides new insights into the effect of grass A pollen exposure, at birth and shortly

after, being responsible for possible allergic respiratory diseases. Three birth cohort studies based in Australia, Denmark and Germany conducted by Susanto et al,from La Trobe University, analyzed the umbilical cord blood collected from hundreds of babies born during and soon after peak grass pollen season.

Immunoglobulin E (IgE), which is used as a marker to predict the

Scientists find more than 500 new genes allied to BP recent study unveils new gene areas conferring blood pressure A traits, helping understand the biological pathway for blood pressure regulation and thereby controlling the major risk factors like heart attack or stroke associated with it. The study was conducted by a group of researchers from Queen Mary University of London (QMUL) and Imperial College London.

The researchers analyzed DNA of more than 1 million people, which revealed 535 new genetic loci linked with blood pressure traits. The scientists found that all of the genetic variants identified were shown to increase a personâ&#x20AC;&#x2122;s risk of high blood pressure by 3.34 times, and that people in the higher genetic risk group exhibited a 1.52 times higher possibility to suffer from consequent cardiac diseases.

60 / FUTURE MEDICINE / OCTOBER 2018

development of allergic diseases, were found to be higher in cord blood of babies born during grass pollen seasonsin cities from both hemispheres. But increased pollen loads in the environment during the entire pregnancy appeared protective, which indicates possible development of a sensitization barrier. Thus, the study focused on the effect of pollen exposure in utero, which was previously a mere suspected concept relating to respiratory disorders. The

The researchers suggest that knowing the genes responsible for high blood pressure may help us to spot the people who are at risk before the damage is done, so that they can be prognosticated earlier and therefore can be administered for implementing a healthy lifestyle to prevent the adverse consequences. The study also indicates potential new targets for drug development, suggesting that some drugs like canagliflozin prescribed for other diseases like type2 diabetes could be repurposed for

researchers also stressed the fact that not all babies born during the high pollen seasons developed respiratory diseases or other allergies. They also emphasized the need for more research to be done, though the current study helps predict and manage diseases like asthma which are relevant public health burden.

Source: https://www.sciencedirect.com/ science/article/pii/S0160412017320469

treating hypertension due to similar gene regions targeted by the drug.

The identification of a new biological pathway for blood pressure regulation therefore potentiates improved cardiovascular disease prevention in future. The study reports to be the largest genetic association study of blood pressure traits to date.

Source: https://www.sciencedaily.com/ releases/2018/09/180917111619.htm

â&#x20AC;&#x153;Lab-in-a-dropâ&#x20AC;? tech: Way to detect deadly diseases from home new medical breakthrough, which could diagnose millions A via a completely portable home

kit, has been designed to detect how likely a person is to suffer from grave diseases like cancer and other ailments. Xing Technologies Pty Ltd developed this nanodiagnostic

technology, claimed to be a game changer, which would enable rapid, point-of-care diagnosis, screening and ongoing monitoring of cancer and other diseases like tuberculosis, heart diseases, diabetes and Alzheimer’s, without requiring access to laboratory facilities and highly trained personnel.

The technology convenes a whole laboratory into a single cartridge which can perform the tests. Each cartridge has a specific application, either to diagnose a cancer or an infectious disease. A sample of the patient’s urine, sputum or blood is inserted into the cartridge and analysed via its portable reader.

Results are transmitted to a cloud software platform and a report is then transmitted back to the doctor, nurse or healthcare worker. The kit is

in insulin resistant adipocyte models developed from human mesenchymal stem cells (hMSC). The study found that overexpression of miR-876-3p in insulin resistant cells decreased

the adiponectin hormone levels, which elevated insulin resistance by altering specific performed adipokine expression. Lentivirus-mediated overexpression and suppression studies were performed in insulinresistant adipocytes differentiated from hMSC and high fat-diet fed C57BL/6 obese mice models to validate the findings in vivo, which were shown to ameliorate insulin resistance with inhibition of miR-876-3p. The study provides a new perspective and the findings show greater implications in the development of therapeutic targets for type-2 diabetes.

Source: Bioscientifica.com Journal of Endocrinology (2018) 239, 1–17 https:// doi.org/10.1530/JOE-17-0387

Targeting senescent cells may promote memory restoration recent research shows causal link between senescent cells and A neurodegenerative disease, suggesting

currently designed to be sent to third world countries, and communities in regional Australia, and promises to be a revolutionary, life-saving technology.

Source: https://xingtech.com.au/xing-media/ media-releases https://www.9news.com.au/videos/ cjm8y9sg9000j0goyupfjy9xe/medicalbreakthrough-could-change-diagnosis-process

that targeting the former may provide a therapeutic avenue for the treatment of these pathologies. Mayo Clinic researchers, involving J. Bussian et al, found that senescent cells, on elimination from naturally aged mice, were found to extend their healthy life span. These cells accumulate with advancing natural age at sites related to diseases of aging, including osteoarthritis and atherosclerosis; and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s.

The researchers used a mouse model afflicted with tau-dependent neurodegenerative disease, which accumulates p16 positive senescent cells showing tangles of tau protein in neurons. Ablation of these cells

using genetically modified, INK-ATTAC transgenic mice model capable of eliminating the senescent cells was shown to prevent the neurofibrillary tangle deposition and degeneration of cortical and hippocampal neurons, thus preserving the cognitive functions, retaining their memory. Thus the study puts forward a best case scenario where prevention of brain damage was shown to avoid the diseased state.

Since a different approach is required for clinical establishment, scientists have started working on models to examine the specific molecular attenuation that occur in the affected cells.

Source:https://www.nature.com/articles/s41586018-0543-y www.sciencedaily.com/ releases/2018/09/180919133024.htm

miRNA alteration to control type-2 diabetes

R

egulation of miRNA becomes a

potential target for therapeutic interventions towards the treatment of type-2 diabetes and obesityassociated metabolic syndrome. miRNA has been increasingly known to play an important role in the regulation of various cellular and metabolic processes. Based on this aspect, a team of scientists from CSIR-CDRI, Lucknow, CSIR-IHBT, Palampur and CSIR-IGIB, New Delhi,investigated the effect of altered expression of miRNA

—Compiled by Divya Choyikutty OCTOBER 2018 / FUTURE MEDICINE / 61

pharma

UNCERTAIN ABOUT VALSARTAN India initiates a probe even as recall of valsartan pills, suspected to be tainted with a potential carcinogenic impurity, continues in leading markets MANJIT BABU

I

n July, India’s drug regulator said the agency was starting an investigation on all companies importing the active pharmaceutical ingredient (API) to make heart drug valsartan from Zhejiang Huahai Pharmaceuticals of China. This unprecedented action by the Drug Controller General of India (DCGI) came in the wake of a recall of the medicines containing valsartan by countries including the US and Germany.

The ongoing probe in the US and Europe to check for the presence of a potential carcinogen in valsartan has put regulators all over the world on high alert. Valsartan, a commonly prescribed angiotensin-II-receptor antagonist (ARB) to manage hypertension, is used for heart failure indication as well.

The DCGI’s announcement prompted drug control offices in the country to be vigilant on the import of the raw materials for the drug. The drug regulator said all port offices were asked to check the consignments imported into the country and conduct tests on each batch to address the issue.

Even as Indian manufacturers Torrent Pharmaceuticals and Hetero Drugs voluntarily withdrew their valsartan

62 / FUTURE MEDICINE / OCTOBER 2018

drugs from the US market, latest reports indicate that India’s Central Drug Standard Control Organisation (CDSCO), the top regulator’s office, has assured that the ingredient that is suspected to have the impurity is not present in the drugs available in India.

NDMA: The suspect The entire issue came to the fore when Prinston Pharmaceuticals, Inc. contacted

ZHEJIANG HUAHAI HAD DETECTED AN IMPURITY – A CHEMICAL KNOWN AS N-NITROSODIMETHYLAMINE (NDMA) ­— IN THE VALSARTAN API.

the USFDA’s Center for Drug Evaluation and Research (CDER) about some of its products containing valsartan API manufactured by Zhejiang Huahai Pharmaceutical Co. (ZHP), on 19th June, 2018.

Prinston informed CDER that they had stopped making valsartan products because ZHP had detected

an impurity – a chemical known as N-nitrosodimethylamine (NDMA) -- in the API. NDMA is a probable cancercausing chemical found in trace amounts in water and some foods. The levels of NDMA in ZHP’s valsartan API, though only in trace amounts, were unacceptable.

“Although the risk to patients taking the affected products is extremely low, we take matters of pharmaceutical quality very seriously.

We took immediate steps to address these findings,” said a statement from FDA Commissioner Scott Gottlieb, M.D., and Janet Woodcock, M.D., director of the Center for Drug Evaluation and Research, on FDA’s ongoing investigation into valsartan impurities and recalls.

The US drug regulator is closely coordinating with the European

Medicines Agency (EMA), European Directorate for the Quality of Medicines (EDQM), Regulatory Operations and Regions Branch and Therapeutic Products Directorate of Health Canada, and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, sharing the developments on the investigation.

International regulators have since identified another API manufacturer, Zhejiang Tianyu Pharmaceutical Co., with NDMA in its valsartan API. The USFDA said that no valsartan products in the US market use this API. The FDA estimates that if 8,000 people took the highest valsartan dose (320 mg) from NDMA-affected medicines daily for four years (the amount of time it believes the affected products have been on the U.S. market), there may be one additional case of cancer over the lifetimes of these 8,000 people beyond the average cancer rate among Americans.

“This estimate represented the highest possible level of NDMA exposure. It was a measure of the risk under the most extreme circumstances.

Most patients who were exposed to the impurity through the use of valsartan received less exposure than this worstcase scenario,” it said.

Difficult to determine NDMA’s properties make it difficult to find. To determine if valsartan products do contain this impurity, CDER’s scientists have developed the gas chromatography-mass spectrometry (GC/MS) headspace testing method.

It has posted this method to the web to help manufacturers and regulators detect NDMA in valsartan API and tablets.

“Specifically, a combination of conditions, which include certain chemicals, processing conditions and production steps, could lead to the formation of the NDMA impurity. We believe that these risks are introduced through a specific sequence of steps in the manufacturing process, where certain chemical reactions are needed to form the active ingredient.

Before we undertook this analysis,

USFDA finds second impurity T he US FDA has found an additional unexpected impurity N-Nitrosodiethylamine (NDEA) in the active pharmaceutical ingredient (API) valsartan.

NDEA, a known animal and suspected human carcinogen, was found in three lots of Torrent Pharmaceuticals’ recalled valsartan drug products, the USFDA said while updating the public on the agency’s ongoing investigation surrounding the recent voluntary recall of several drug products containing valsartan API. These Torrent products were included in the company’s recall on August 23, 2018 Like N-Nitrosodimethylamine (NDMA), which was found in the recalled valsartan products, NDEA is also formed from a specific sequence

IF 8,000 PEOPLE TOOK THE HIGHEST VALSARTAN DOSE (320 MG) FROM NDMAAFFECTED MEDICINES DAILY FOR FOUR YEARS, THERE MAY BE ONE ADDITIONAL CASE OF CANCER OVER THEIR LIFETIMES, THE FDA ESTIMATES.

neither regulators nor industry fully understood how NDMA could form during this process,” said the FDA officials.

The US drug watchdog has been conducting a review of ARBs from 2010, according to the documents. In light of the valsartan issue, the FDA is conducting a study on all ARBs to check for the presence of NDMA.

Low risk potential?

The EMA officials in August said that the NDMA levels detected in batches of valsartan from Zhejiang Tianyu are much lower than the levels seen in the active substance from Zhejiang Huahai, which

of manufacturing steps and chemical reactions.

In addition to the FDA’s testing, the agency will post a preliminary method for detecting NDEA. Manufacturers and global regulators can use this method to screen other products for the potential presence of this impurity.

triggered a recall of several valsartan medicines in July 2018.

While the DCGI assures that the contaminated batches of the ingredient has not touched Indian shores, experts say that there are alternatives available for the drug and that doctors can switch to other products in order to avoid any possible risk.

In India, valsartan is available as a single drug as well as in fixeddose combinations. Patients taking this drug should not stop the drug without consulting their doctors for two reasons: First, not all valsartan containing products are recalled and second, many equally efficacious alternatives to valsartan are available, alert experts. "Physicians should take caution prescribing drugs containing valsartan unless they can confirm that the particular API is not sourced from the companies mentioned above,'' says Dr Anoop Agrawal, Consultant, Interventional Cardiology, CARE Hospitals, Hyderabad. FDA has listed the recalled manufacturers on their website.

He suggests that in India, authorities should aggressively test the available drugs for the said impurity and put out our own list of recalled and not-recalled brands.

OCTOBER 2018 / FUTURE MEDICINE / 63

hospital news

Aster DM partners with Nigerian university hospital A CK Birla Hospitals-CMRI conducts sepsis programme

C

K Birla Hospitals – Calcutta Medical Research Institute (CMRI) conducted a comprehensive sepsis management programme in Eastern India on the occasion of World Sepsis Day. Organised in association with the Indian Sepsis Forum, Hospital Infection Society of India, SEMI WB chapter and Indian Society of Critical Care Medicine (ISCCM), the initiative enlightened the clinicians about the ways to combat sepsis in a holistic manner.

The Basic Sepsis Life Support Programme (BSLS), which included an in-depth review of sepsis along with its management and practical application required for dealing with patients suffering from sepsis, shared clinical knowledge, management guidance and organisation skills with doctors, nurses and healthcare personnel to improve clinical outcome.

India currently tackles 7,50,000 cases of sepsis every year, in which the mortality rate is 12.08 per cent in ICU patients and 59.26 per cent in those with critical stage sepsis. More than 90,000 people die every year in India due to sepsis, making it one of the most alarming causes of death in the country, according to Dr Arindam Kar, director & HOD, critical care unit, CK Birla Hospitals - CMRI. Every year, World Sepsis Day is celebrated internationally on 13 September with awareness campaigns to facilitate a more comprehensive outlook into the management of sepsis.

The BSLS programme was one such national level initiative which promised to mark the beginning of a more inclusive, updated and evidence-based approach to tackle the severity and life-threatening situations caused by sepsis.

64 / FUTURE MEDICINE / OCTOBER 2018

ster DM Healthcare has entered into a partnership agreement with Afe Babalola University Ado Ekiti (ABUAD), a leading university hospital in Nigeria.

As part of the deal, Aster would set up centres of excellence across specialties in association with ABUAD to address the need gaps in the Nigerian healthcare sector.

Aster Centers of Excellence provide quaternary care across various specialties such as neuroscience, cardiac, orthopaedic and oncology.

The agreement also aims to build a telemedicine unit managed by Aster DM Healthcare’s certified specialists chosen from Aster’s network of 11 hospitals in India.

The telemedicine unit in ABUAD

will provide services such as tele consulting, tele diagnosis and tele management, enabling patients to seek expert advice and virtual treatment from Aster’s specialists from across the world, including in India.

Nigeria spends an average of US$ 118 per capita on healthcare.

In terms of the doctor-patient ratio, Nigeria currently has 1:2,500, as opposed to a minimum ratio of 1:1000 recommended by WHO. “Our partnership will address the gaps in the healthcare sector in Nigeria which is in urgent need of quality services,'' said Dr Azad Moopen, founder chairman and managing director of Aster DM Healthcare, in a press release.

BR Life SSNMC and Brains Neuro set up CoE

B

R Life SSNMC Super Speciality Hospital, Bengaluru, has joined hands with Brains Neurosciences to establish a Centre of Excellence (CoE).

Located at Ideal Homes Layout, Rajarajeshwari Nagar, Bengaluru, the centre will provide comprehensive diagnosis, treatment and rehabilitation services for brain and spine related problems.

In addition to this, there will be specialty clinics for the management of stroke, headache, dementia, epilepsy, Parkinson’s and Alzheimer’s. A fully equipped neurotrauma center for

trauma and head injury treatment will be operational 24x7.

The CoE has set-up the Brain Wellness Clinic to facilitate early detection of Alzheimer’s disease.

Early diagnosis, prevention and identification of treatable dementias as a therapy goal can help provide effective treatment and improve the living conditions of the patient, according to Dr Venkataramana NK, head, SSNMC-Brains Neurosicience Center of Excellence.

BR Life SSNMC Super Specialty Hospital is promoted by Dr BR Shetty, an Abu Dhabi-based Indian entrepreneur.

head&neck cancer

REVISED AJCC TNM GUIDELINES

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

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

T

he American Joint Committee on Cancer (AJCC), 8th Edition marks a major change in the Tumour Nodal Metastasis (TNM) staging of head‑and‑neck cancers. It introduces many new concepts to stage and prognosticate patients better, with distinct therapeutic implications.

In oral cancer, it introduces the depth of invasion as a determinant of T(tumour)‑stage. This standardises the staging of oral cancer tumours and acknowledges the significance of depth of invasion in nodal spread and overall survival. It also eliminates “extrinsic muscle invasion” from stage T4 for oral tongue cancer; this was a constant source of confusion since the depth of invasion required to involve the extrinsic muscles of the tongue was highly variable depending on the position of the tumour in relation to the tongue. Even very superficial tumours could invade the extrinsic muscles of the tongue. The nodal staging recommendations have also upstaged extranodal extension, which has been shown to be a high‑risk adverse feature associated with worse survival.

In oropharyngeal cancer, human papillomavirus (HPV) expression of tumours has been used to reclassify tumours into two separate entities with distinct staging systems. For HPV‑positive tumours (p16 positive), the T‑stage no longer has T4b, or very advanced local disease, which represents the improved prognosis that these patients have when compared to their non‑HPV counterparts. For 66 / FUTURE MEDICINE / OCTOBER 2018

HPV‑positive tumours, nodal staging has been divided into clinical staging and pathological staging for better prognostication of HPV‑positive diseases treated with surgery.

In carcinoma of unknown primaries with cervical nodal metastasis, immunohistochemical staining of nodal tissue for HPV and Epstein–Barr virus (EBV) has been recommended in all cases. This recognizes the high incidence of metastasis from an HPV‑positive oropharyngeal or an EBV‑positive nasopharyngeal primary tumour, and the need to standardize the diagnostic evaluation in these patients to avoid inadequate evaluation and inappropriate treatment.

These recommendations are

based on high‑quality evidence aimed at personalizing cancer therapy to optimize outcomes, while minimizing morbidity. The practice of oncology in India, however, is markedly different from that in the western world.

India spends a small fraction (under 2%) of its gross domestic product on health‑care services, with an estimated 65% of all healthcare‑related expenditure being spent out‑of‑pocket.

This results in a clear majority of patients with cancer receiving an insufficient quality and standard of care.

This context of resource constraint has a significant impact on the practice of resource‑heavy medical specialties such as oncology, where newer diagnostic and therapeutic techniques are often

ORAL CANCER STAGING BY DEPTH OF INVASION

New guidelines standardise the staging of oral cancer tumours and acknowledges the significance of depth of invasion in nodal spread and overall survival.

T1

invasion 5 mm or less

T3

T4b

20 and more than 20

more than 10 and less than 20mm

T2

invasion 6-10 mm

out of reach for many patients in developing countries.

Depth of invasion in oral cancers Tumours having a depth of invasion of 5 mm or less are classified as T1, those having a depth of invasion 6–10 mm are classified as T2, and those with a depth of invasion higher than 10 mm and less than 20 mm are classified as T3. Tumours more than 20 mm depth or crossing the midline are T4b cancers.

The subjectivity and interobserver variability in determining the clinical depth of invasion may be challenging.

For those treated with surgery, the measurement of the depth of invasion is pathological, where a plumb line is dropped from the adjacent mucosa to the deepest point of tumour invasion.

The issue with this parameter, as seen in other malignancies, is the interobserver variability; studies have shown a variable concordance rate among pathologists with respect to the depth of invasion.

A significant number of patients with oral cancer in India are treated with radiotherapy, either as brachytherapy or external beam radiotherapy. The measurement of the depth of invasion in these patients poses a bigger challenge, and there is no consensus on radiological determination of the depth of invasion in oral cancer.

Nodal staging in oropharyngeal cancer For HPV‑positive oropharyngeal cancer, clinical nodal staging is now similar to the nodal staging for nasopharyngeal cancer: N1 is one or more ipsilateral nodes with none >6 cm, N2 is contralateral or bilateral lymph nodes with none >6 cm, and N3 comprises nodal disease >6 cm. Pathological staging is N1 when metastasis occurs to ≤4 lymph nodes. N2 is when metastasis occurs to >4 lymph nodes. This is meant to better prognosticate HPV‑related oropharyngeal cancers at two distinct points – with a clinical determination of staging at presentation, and a definitive pathological staging following surgery. This is most likely

OROPHARYNGEAL CANCER NODAL STAGING Clinical nodal staging is now recommended for HPV-positive oropharyngeal cancer

CATEGORY CRITERIA

N1

N2

N3

One or more ipsilateral lymph nodes, none larger than 6 cm

Contralateral or bilateral lymph nodes, none larger than 6 cm

Lymph node(s) larger than 6 cm

THE TECHNICAL EXPERTISE AND EQUIPMENT REQUIRED TO PERFORM ROUTINE IMMUNOHISTOCHEMISTRY ARE LACKING IN MANY CENTRES THAT PROVIDE CANCER CARE IN INDIA.

a reflection of the increasing use of transoral robotic surgery (TORS) in the treatment of oropharyngeal cancer in the United States. Access to TORS, however, has been shown to correlate with socioeconomic status even in a developed country; and the number of patients with head‑and‑neck cancer in India with access to TORS is minuscule.

Unknown primary For patients with squamous cell carcinoma demonstrated in cervical lymph nodes without any demonstrable primary site of malignancy, strong recommendations have been made regarding the addition of immunohistochemistry to the diagnostic evaluation. Acknowledging that around 90% of all unknown primaries are associated with an HPV‑related oropharyngeal cancer in the United States, the AJCC has recommended that HPV in situ hybridization, p16 immunohistochemistry, and

EBV‑encoded RNA in situ hybridization be performed for all unknown primaries of the cervical lymph nodes. Whether this recommendation is feasible in an Indian context is debatable; the number of unknown primaries associated with HPV in India is likely to significantly fewer when compared to that of the West. The technical expertise and equipment required to perform routine immunohistochemistry and techniques such as in situ hybridization are also lacking in many centres that provide cancer care in India.

In short, the new recommendations made by the AJCC 8th Edition for the treatment of head‑and‑neck cancers address many of the shortcomings of the previous editions. The majority of these recommendations are universal.

However, some are likely to face hurdles in their implementation in India. The recommendations represent a step toward standardization in radiological and pathological reporting. However, the degree of compliance that can be attained to these recommendations remains to be seen.

The author is Professor, Department of Head and Neck Surgery and Oncology Amrita Institute of Medical Sciences, Kochi, India

drkrishnakumart@gmail.com OCTOBER 2018 / FUTURE MEDICINE / 67

insurance

INSURANCE COVER FOR INFERTILITY TREATMENT Infertility treatment may soon be made part of standard insurance policies DR DURU SHAH

I

nfertility is fast becoming a huge concern in India. With 30 million infertile couples currently, it is estimated that in the year 2020, 2,50,000 IVF cycles will be performed in the country. Needless to say, the cost of infertility treatments too continues to rise, making it unaffordable to a large number of couples. There is a huge need for the government to make necessary budgetary provisions and insurance companies to cover infertility procedures as well.

The Indian Society for Assisted Reproduction (ISAR) had last year strongly campaigned with insurance companies and the government to make necessary provisions to bring infertility treatment under insurance cover in India. The change has now been brought about by the efforts of the Govt of India, especially the division heading the Ayushman Bharat programme, and the Insurance Regulatory Authority of India.

In August 2018, the Insurance and Regulatory Authority of India (IRDAI), asked for the removal of around 10 items, including procedures such as dental, stem cell, infertility and psychiatric treatment, from the list of “optional cover” for health insurance.

This would mean that these procedures could be made part of standard insurance policies. Some of them could even be made mandatory! It is heartening to note that infertility has been included in this list—the fact that the Indian insurance sector will now provide insurance cover for infertility treatment will definitely make it more affordable to the millions of couples

68 / FUTURE MEDICINE / OCTOBER 2018

ISAR HAD LAST YEAR STRONGLY CAMPAIGNED WITH INSURANCE COMPANIES AND THE GOVERNMENT TO MAKE NECESSARY PROVISIONS TO BRING INFERTILITY TREATMENT UNDER INSURANCE COVER. who need it.

ISAR had proposed to the Ministry of Health and Family Welfare to make infertility treatment easier for couples seeking treatment for infertility by having it covered under their health insurance plan. And now, with the Ministry of Health considering this proposal, the efforts are bearing fruit.

Research has shown that one in every six couples has a problem conceiving on their own, which is a clear indication of the large number of people who need assistance to fulfill their need to have children. Very often, simple advice or a little help from the gynecologists can help them in their pursuit of having their own biological

child. But, occasionally they require advanced procedures like IVF, ICSI, egg donation, etc. While simpler treatments are manageable and affordable with every gynecologist, advanced procedures need to be undertaken at centres that offer assisted reproduction.

However, the fact is that the cost of IVF ranges upwards of ₹1.5 lakh to ₹2 lakh per cycle of treatment, mainly because the cost of the consumables used for IVF and the expenditure involved in maintaining a high-quality embryology lab are high. Hence, a huge number of couples desist from seeking treatment or resort to poor-quality care. Infertility treatment not only involves expenditure, but it also involves a huge amount of investment from the couple seeking treatment. This includes daily injections, the time spent on treatment, giving up on their careers due to frequent visits to the clinic, financial loss, mental agony, and many a times, disappointment when the pregnancy test is negative after such a long ordeal.

Their journey while seeking infertility treatment will definitely be easier now, thanks to IRDAI’s change in policy. We will soon begin to see the effect of this change in the number of patients seeking affordable medical treatment for infertility. In addition, if India can reduce the dependence on imported consumables for infertility procedures by manufacturing them, we will be able to make IVF much more affordable.

The author is Director, Gynaecworld Center for Assisted Reproduction & Women’s health Panel Consultant – Breach Candy Hospital & Jaslok Hospital, Mumbai.

Ultrasound

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health care

INDIA LAUNCHES WORLD’S LARGEST PUBLIC FUNDED HEALTHCARE SCHEME Industry lauds Ayushman Bharat, but says there are areas that need focus

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ndia, a country of 1.3 billion people with just a fraction of them covered under medical insurance, has kickstarted the world’s largest public funded healthcare programme -- Ayushman Bharat - Pradhan Mantry Jan Arogya Yojana. The scheme is expected to benefit around 10 crore economically backward families with an annual healthcare coverage of Rs 5 lakh each and aims to cover around 550 million people across the country.

As announced on the country’s 71st Independence Day in August, Prime Minister Narendra Modi launched the programme on September 23 in Jharkhand. Launching the scheme at the state capital Ranchi, the Prime Minister said: “It is a big step towards providing good quality and accessible healthcare to the poor of India.”

As per the nationwide launch plan, nearly 31 states and Union Territories will implement the programme now. As part of the launch, the Prime Minister also inaugurated 10 wellness centres in Jharkhand.

“The government is pursuing a holistic approach towards the betterment of the health sector. As

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it focuses on affordable healthcare on one hand, emphasis is also being laid on preventive healthcare on the other,” Modi said, while launching the programme.

“This is the world’s largest such scheme and the number of Ayushman

THE SCHEME WILL BE FUNDED WITH 60% CONTRIBUTION COMING FROM THE CENTRAL GOVERNMENT AND THE REMAINING FROM THE STATES.

Bharat beneficiaries is almost equal to the population of Canada, Mexico and the US put together,” Modi added.

The scheme became operational on September 25 on the birth anniversary of Pandit Deendayal Upadhyay and will be funded with 60% contribution

coming from the central government and the remaining from the states. Five states, including Telangana, Odisha, Delhi, Kerala and Punjab, are yet to sign the agreement on the scheme with the centre.

Eligible people can avail the benefits in government and listed private hospitals. The beneficiaries are identified based on mainly four “deprivation” categories. They need to establish their identity to avail benefits under the scheme and it could be through Aadhaar card or election ID card or ration card.

In case of hospitalisation, members of the beneficiary families do not need to pay anything, provided they go to a government or an empanelled private hospital.

Even as the healthcare industry welcomed the historical launch of the scheme, it reminded the government that there are areas that need to be addressed to ensure that such a large-scale health-cover programme is successfully implemented.

“On the historic launch of the world’s largest health coverage scheme - Ayushman Bharat, I feel as happy as I

did when we launched the first universal insurance scheme in my village in the year 1999. I am also filled with a sense of anticipation on the positive effect this scheme will have on the health of the 50 crore beneficiaries,”said Pratap C Reddy, founder and chairman of the country’s largest corporate hospital chain, Apollo Hospitals.

“While we all work together to ensure the success of this scheme, there are areas that need focus and fine tuning. These include ensuring the robustness of the IT backbone, weeding out potential fraud, ensuring coverage to only identified beneficiaries and ensuring more adoption by the private sector, who are rightly worried about the pricing and reimbursements. These issues must remain paramount moving forward,”he said, adding that he strongly believes that the scheme is for the greater public good and everyone must strive to ensure its success.

Earlier, after the first announcement of the programme in August, Tedros Ghebreyesus, Director General of World Health Organisation, lauded the initiative by the government of India, calling it a great commitment.

However, healthcare industry

consultants have expressed concerns about the lack of clarity in the budgetary allocation and the availability of funds.

There are also concerns about the extent of geographical coverage and the paucity of accredited hospital capacity.

Mumbai-based healthcare industry consultant and Future Medicine columnist Muralidharan Nair had earlier shared his views saying the operational success of the programme will be contingent upon customising the programme to address the ground conditions, which vary significantly from state to state and even within the state.

“This includes the availability of

IT IS IMPERATIVE THAT A COMPLEX PROGRAMME LIKE THIS DEPEND HEAVILY ON TECHNOLOGY SUPPORT FOR EFFECTIVE EXECUTION, BE IT FOR PROCESS EFFICIENCY, PROCESS INTEGRITY, FRAUD PREVENTION ETC.

relevant human resource, the maturity of private providers, public health capability, morbidity profile and the cost of care. I am certain, the learned managers of this programme are fully seized of this matter, but I have a few other concerns too,” he wrote in a previous column.

It is imperative that a complex programme like this depend heavily on technology support for effective execution, be it for process efficiency, process integrity, fraud prevention, optimization strategies or customer feedback. It is unlikely that the technology capabilities will be fully deployed before a while, and importantly, given the rural reach that is planned. Therefore, it is crucial that there is a robust plan for the interim and a sustainable operational ecosystem for carrying out technology operations in the future, Nair added.

The critics of the Central programme say that State cooperation is important for successfully implementing a programme of this scale. Since the many of them are still not in agreement, it may have a negative impact on the nation roll out of the programme.

While Odisha government has already rejected the programme saying the existing state government programme--Biju Swasthya Kalyan Yojana covers many more people than Ayushman Bharat and provides Rs. 7 lakh to women as opposed to the central programme’s Rs. 5 lakh, the Southern state Kerala was critical about the feasibility of the new central programme. Delhi and Telengana states were also in disagreement with Ayushman Bharat. WhileTelangana rejected the scheme on the grounds that its Aarogyasri scheme covers 70 per cent of the state’s population while the Ayushman Bharat will only benefit 80 lakh people, Delhi government said the central programme’s proposed target of 6 lakh families covers just 3 per cent of its 2-crore population.

Similarly, the state of Punjab had also held certain reservations against new health coverage scheme launched by the Centre.

OCTOBER 2018 / FUTURE MEDICINE / 71

public health

A QUARTER OF THE WORLD’S POPULATION HAS TB: WHO Although global efforts have averted an estimated 54 million TB deaths since 2000, TB remains the world’s deadliest infectious disease

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HO’s 2018 Global TB Report calls for an unprecedented mobilization of national and international commitments. It urges political leaders gathering for the firstever United Nations High-level Meeting on TB to take decisive action, building on recent moves by the leaders of India, the Russian Federation, Rwanda, and South Africa. Nearly 50 Heads of State and Government are expected to attend the meeting.

“We have never seen such high-level political attention and understanding of what the world needs to do to end TB and drug-resistant TB, said Dr.Tedros Adhanom Ghebreyesus, WHO Director-

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General. “We must capitalize on this new momentum and act together to end this terrible disease,” in an official release To meet the global target of ending TB by 2030, countries need to urgently accelerate their response – including by

increasing domestic and international funding to fight the disease. The WHO report provides an overview of the status of the epidemic and the challenges and opportunities countries face in responding to it.

TB epidemic: Falling numbers

GLOBALLY, AN ESTIMATED 10 MILLION PEOPLE DEVELOPED TB IN 2017. THE NUMBER OF NEW CASES IS FALLING BY 2% PER YEAR.

Overall, TB deaths have decreased over the past year. In 2017, there were 1.6 million deaths (including among 300 000 HIV-positive people). Since 2000, a 44% reduction in TB deaths occurred among people with HIV compared with a 29% decrease among HIV-negative people; Globally, an estimated 10 million people developed TB in 2017. The number of new cases is falling by 2% per year, although faster reductions have occurred in Europe (5% per year) and Africa (4% per year) between 2013 and 2017.

Some countries are moving faster than others - as evidenced in Southern Africa, with annual declines (in new cases) of 4% to 8% in countries such as Lesotho, Eswatini, Namibia, South Africa, Zambia, and Zimbabwe, thanks to better TB and HIV prevention and care.

In the Russian Federation, high-level political commitment and intensified TB efforts have led to more rapid declines in cases (5% per year) and deaths (13% per year) Drug-resistant TB remains a global public health crisis: In 2017, 558 000 people were estimated to have developed disease resistant to at least

rifampicin â&#x20AC;&#x201C; the most effective first-line TB drug. The vast majority of these people had multidrug-resistant TB (MDR-TB), that is, combined resistance to rifampicin and isoniazid (another key first-line TB medicine).

Under-diagnosis: Big challenge Underreporting and under-diagnosis of TB cases remains a major challenge. Of the 10 million people who fell ill with TB in 2017, only 6.4 million were officially recorded by national reporting systems, leaving 3.6 million people undiagnosed, or detected but not reported. Ten countries accounted for 80% of this gap, with India, Indonesia and Nigeria

topping the list.

Less than half of the estimated one million children with TB were reported in 2017, making it a much higher gap in detection than that in adults.

Treatment coverage lags behind at 64% and must increase to at least 90% by 2025 to meet the TB targets.

To urgently improve detection, diagnosis and treatment rates, WHO, the Stop TB Partnership and the Global Fund launched the new initiative in 2018, Find. Treat. All. #EndTB, which set the target of providing quality care to 40 million people with TB from 2018 to 2022.

Only around half of the estimated 920,000 people with HIV-associated TB were reported in 2017. Of these, 84% were on antiretroviral therapy. Most of the gaps in detection and treatment were in the WHO African Region, where the burden of HIV-associated TB is highest. Only one in four people with

MDR-TB were reported to have received treatment with a second-line regimen.

China and India alone were home to 40% of patients requiring treatment for MDR-TB, but not reported to be receiving it. Globally, MDR-TB treatment success remains low at 55%, often due to drug toxicity making it impossible for patients to stay on treatment. A month ago, WHO issued a Rapid Communication on key changes to treatment of drugresistant TB based on the latest scientific evidence. These changes should result in better treatment outcomes and more lives saved. WHO is already working with countries and partners to roll out these changes.

TREATMENT COVERAGE LAGS BEHIND AT 64% AND MUST INCREASE TO AT LEAST 90% BY 2025 TO MEET THE TB TARGETS.

WHO predicts that at least 30 million people should be able to access TB preventive treatment between 2018 and 2022, based on new WHO guidance.

Although preventive treatment for latent TB infection is expanding, most people needing it are not yet accessing care.

WHO strongly recommends preventive treatment for people living with HIV, and children under 5 years living in households with TB. Related new guidance was issued by WHO in 2018,

to facilitate greater access to preventive services for those who need it.

Insufficient funds One of the most urgent challenges is to scale up funding, the agency said.

In 2018, investments in TB prevention and care in low- and middle-income countries fell US$3.5 billion short of what is needed. The report flags that without an increase in funding, the annual gap will widen to US$ 5.4 billion in 2020 and to at least US$ 6.1 billion in 2022.A further US$ 1.3 billion per year is required to accelerate the development of new vaccines, diagnostics and medicines.

WHO is guiding national and global actions to reach everyone with care, including those with TB, through a transformative health agenda and push towards Universal Health Coverage. This includes proactive engagement with civil society and other key stakeholders to jointly help countries get on track to end TB. Ending the TB epidemic requires action beyond the health sector to address the risk factors and determinants of the disease.

Commitments at the level of Heads of State will be essential to galvanize multisectoral action.

In June this year, an Interactive Civil Society Hearing was organized by the Office of the President of the General Assembly, with the support of WHO, the Stop TB Partnership, civil society, and other stakeholders as a key preparatory step towards high-level meeting, WHO said.

OCTOBER 2018 / FUTURE MEDICINE / 73

medico legal

INDIA RELEASES CHARTER OF PATIENT RIGHTS The draft charter proposes a multi-tier redressal mechanism for patients.

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ndia's health ministry has released the draft statute of the country’s first ‘charter of patients' rights’ to address issues in the healthcare sector.

Prepared by the National Human Rights Commission (NHRC), the draft will act as a guidance

document for the Union government and state governments to formulate concrete mechanisms so that patient’s rights are given adequate protection and operational mechanisms are set up to make these rights functional and enforceable by law.

RIGHTS OF THE PATIENTS AS PER THE DRAFT PATIENT CHARTER

RIGHT TO FACTUAL INFORMATION Every patient has a right to adequate relevant information about the nature, cause of illness, provisional/ confirmed diagnosis, proposed investigations and management, and possible complications To be explained at their level of understanding in a language known to them. The treating physician has a duty to ensure that this information is provided in simple and intelligible language to the patient to be communicated either personally by the physician, or by means of his / her qualified assistants.

Every patient and his/her designated caretaker have the right to factual information regarding the expected cost of treatment based on evidence.

The hospital management has a duty to communicate this information in writing to the patient and his/her designated caretaker.

RIGHT TO RECORDS AND REPORT The relatives/caregivers of the patient have a right to get discharge summary or in case of death, death summary

along with original copies of investigations.

The hospital management has a duty to provide these records and reports and to instruct the responsible hospital staff to ensure the provision of the same are strictly followed without fail.

RIGHT TO EMERGENCY MEDICAL CARE It is the duty of the hospital management to ensure the provision of such emergency care through its doctors and staff, rendered promptly without compromising on the quality and safety of the patients.

RIGHT TO INFORMED CONSENT It is the duty of the hospital management to ensure that all concerned doctors are properly instructed to seek informed consent, that an appropriate policy is adopted and that consent forms with

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the protocol for seeking informed consent are provided for patients in an obligatory manner.

It is the duty of the primary treating doctor administering the potentially hazardous test/ treatment to explain to the patient and caregivers the main risks that are involved in the procedure, and after giving this information, the doctor may proceed only if consent has been given in writing by the patient/caregiver or in the manner explained under Drugs and Cosmetic Act Rules 2016 on informed consent.

RIGHT TO CONFIDENTIALITY, HUMAN DIGNITY, AND PRIVACY All female patients have the right to the presence of another female person during physical examination by a male practitioner. It is the duty of the hospital management to ensure the presence of such female in the case of female patients.

RIGHT TO SECOND OPINION Every patient has the right to seek the second opinion from an appropriate clinician of patients’ / caregivers’ choice.

The hospital management has

a duty to respect the patient’s right to second opinion, and should provide to the patients caregivers all necessary records and information required for seeking such opinion without any extra cost or delay.

RIGHT TO TRANSPARENCY IN RATES Every patient has a right to receive health care services within the range of rates for procedures and services prescribed by Central and State Governments from time to time, wherever relevant.

However, no patient can be denied choice in terms of medicines, devices and standard treatment guidelines based on the affordability of the patients’ right to choice.

RIGHT TO NONDISCRIMINATION The hospital management must regularly orient and

instruct all its doctors and staff regarding the same.

The hospital management has a duty to ensure that no form of discriminatory behaviour or treatment takes place with any person under the hospital’s care.

RIGHT TO SAFETY AND QUALITY CARE ACCORDING TO STANDARDS The hospital management has a duty to ensure the safety of all patients in its premises including clean premises and provision for infection control guidelines and to avoid medical negligence or deficiency in service.

RIGHT TO CHOOSE THE SOURCE FOR OBTAINING MEDICINES OR TESTS When any medicine is prescribed by a doctor or a hospital, the patients and their caregivers have the right to choose any registered pharmacy of their choice to purchase them.

RIGHT TO CONTINUITY OF CARE The patient and caregivers have the right to be informed by the hospital about any continuing healthcare requirements following discharge from the hospital.

The hospital management has a duty to ensure proper referral and transfer of patients regarding such a shift in care.

RIGHT TO TAKE DISCHARGE OF THE PATIENT, OR RECEIVE THE BODY OF DECEASED FROM THE HOSPITAL A patient has the right to take a discharge and cannot be detained in a hospital, on procedural grounds such as a dispute in payment of hospital charges. Similarly, caretakers have the right to the dead body of a patient who had been treated in a hospital and the dead body cannot be detailed on procedural grounds, including nonpayment/dispute

regarding payment of hospital charges against wishes of the caretakers.

RIGHT TO CHOOSE ALTERNATIVE TREATMENT OPTIONS IF AVAILABLE In case a patient leaves a healthcare facility against medical advice on his / her own responsibility, then notwithstanding the impact that this may have on the patient’s further treatment and condition, this decision itself should not affect the observance of various rights mentioned in this charter.

RIGHT TO PATIENT EDUCATION The hospital management and treating physician have a duty to provide such education to each patient according to standard procedure in the language the patients understand and communicate in a simple and easy to understand manner.

RIGHT TO BE HEARD AND SEEK REDRESSAL Patients and caregivers have the right to seek redressal in case they are aggrieved, on account of infringement of any of the above-mentioned

rights in this charter. This may be done by lodging a complaint with an official designated for this purpose by the hospital/healthcare provider and further with an official mechanism constituted by the government such as Patients’rights Tribunal Forum or Clinical establishments regulatory authority as the case may be.

Every hospital and clinical establishment has the duty to set up an internal redressal mechanism as well as to fully comply and cooperate with official redressal mechanisms including making available all relevant information and taking action in full accordance with orders of the redressal body as per the Patient’s Right Charter or as per the applicable existing laws.

RIGHT TO PROTECTION FOR PATIENTS INVOLVED IN CLINICAL TRIALS RIGHT TO PROTECTION OF PARTICIPANTS INVOLVED IN BIOMEDICAL AND HEALTH RESEARCH

OCTOBER 2018 / FUTURE MEDICINE / 75

ethics

perspectives

DOCTORS OWE A CONSTITUTIONAL DUTY TO TREAT THE HAVE-NOTS: SC The Supreme Court of India has observed that a doctor cannot refuse treatment to a person merely on the ground that he cannot afford it

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ndiaâ&#x20AC;&#x2122;s Supreme Court, while deliberating on the case pertaining to the Delhi governmentâ&#x20AC;&#x2122;s circular to hospitals built on subsidised land, has observed that members of the medical profession owe a constitutional duty to treat the

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poorer sections of the society.

Doctors cannot refuse to treat a person who is in dire need of treatment by a particular medicine or by a particular expert merely on the ground that he is not in a position to afford the fee payable for such an

opinion or treatment, the court ruled.

Setting aside the Delhi High Court order that had dismissed the circular issued by the Delhi government, the SC bench directed all the hospitals in Delhi to go by the conditions imposed by the government.

What the Supreme Court said

D

escribing the denial of proper treatment to a person belonging to the lower economic strata of the society as inhuman, Justice Arun Mishra made some observations about medical profession and ethics in his 124-page judgement.

THE COURT UPHELD THE DELHI GOVERNMENT CIRCULAR SAYING THAT STIPULATION FOR FREE TREATMENT DOES NOT AMOUNT TO RESTRICTION UNDER ARTICLE 19(6) ON THE RIGHT ENSHRINED UNDER ARTICLE 19(1)(G).

The circular issued by the Government of NCT of Delhi had asked the hospitals built on subsidized land to provide free treatment to 10% indoor patients and 25% outdoor patients from the economically backward people.

The court upheld the Delhi government circular saying that such stipulation for free treatment does not amount to restriction under Article 19(6) on the right enshrined under Article 19(1)(g).

The bench also directed the government to file periodic reports for one year on the compliance of the conditions by hospitals in Delhi.

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 Medical profession deals with the life of human beings. There has to be a balancing of human rights with the commercial gains.  Members of the medical profession owe a constitutional duty to treat the have-nots. They cannot refuse to treat a person who is in dire need of treatment by a particular medicine or by a particular expert merely on the ground that he is not in a position to afford the fee payable for such an opinion/treatment.

The moment it is permitted, the medical profession would become purely a commercial activity. It is not supposed to be so due to its nobleness.  It would be inhuman to deny a person who is not having sufficient means, or no means, to afford life-saving treatment, simply on the ground that he is not having enough money. If treatment is refused due to financial reasons, it would be against the very basic tenets of the medical profession and the concept of charity in whatever form we envisage the same. Besides being unconstitutional, it would be violative of basic human rights.  By and large, hospitals have now become centres of commercial exploitation and instances have come to notice when a dead body is kept as security for clearance of bills, which is per se illegal and a criminal act. In future, whenever such an act is reported to the police, it is supposed to register a case against the management of the hospital and all concerned doctors involved in such an inhumane act which destroys the basic principles of human dignity and

is tantamount to a criminal breach of the trust reposed in the medical profession.

The state spends and invests a huge amount of public money on the making of a doctor, and it is the corresponding obligation on the part of the doctor to serve the needy. Treatment cannot be refused on the ground of financial inability of the patient.  Besides wrong reporting, uncalled for investigation -- inclusive of invasive tests on the heart and other parts of the body, which are wholly unnecessary -- are performed. It is time for soul-searching for big hospitals in and around Delhi, Gurgaon and other places. They must ponder what they are doing. Is it not a criminal act? The fact that action is not taken does not absolve them of the responsibility. Time has come to fix accountability and to set right the evils which have rotten the system. The medical profession had never been intended to be an exploitative device to earn money at the cost of the patients who require a godly approach and the helping hand of doctors. Every prescription starts from Rx, not from the amount of bill. Big commercial international hospitals, are not above the ethical standards which they have to maintain at all costs, including by extending financial help to the have-nots.  The hospitals nowadays have five-star facilities. The entire concept has been changed to make commercial gains. They are becoming unaffordable. The charges are phenomenally high, and at times unrealistic compared with the service provided. The dark side of such hospitals can be illuminated only by the sharing of the obligation towards economically weaker sections of the society. It would be almost inhuman to deny proper treatment to the poor owing to economic conditions.

devices&gadgets

MRI-compliant cochlear implant cleared in US H

Once-weekly exenatide pen gets EC nod

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he European Commission (EC) has approved Bydureon BCise (exenatide 2mg prolonged-release suspension for injection in prefilled pen) for the treatment of patients with type-2 diabetes.

The new formulation of once-weekly Bydureon is an improved single-dose, pre-filled pen device that requires no titration and is approved for use in combination with other glucose-lowering medicines, said AstraZeneca, the maker of the device.

The EC approval is based on the data from two clinical trials, Duration-Neo-1 and Neo-2. Duration-Neo-1 is a 28-week, randomised, openlabel, comparator-controlled trial (n=375), which showed that once-weekly Bydureon BCise demonstrated an HbA1c reduction of 1.4% vs. 1.0% for twice-daily Byetta (exenatide) injection at 28 weeks (baseline HbA1c 8.5% and 8.4%, respectively). Additionally, Bydureon BCise demonstrated a mean weight reduction of -1.5 Kg as monotherapy vs. -1.9 Kg (baseline was 97 Kg) when combined with certain oral antidiabetic medicines.

This new formulation of once-weekly Bydureon BCise was approved by the US FDA in October 2017.

iRes Ultra 3D cochlear implant, produced by Advanced Bionics, has received clearance from the USFDA. The new magnet design provides alignment with an external magnetic field in any direction. This allows cochlear implant recipients to move freely around in the strong magnetic field of an MRI machine without feeling pain or discomfort, and without restrictions to the orientation of the head. Even for high resolution MRI examinations, there is no need to remove the magnet and no requirement for head bandaging, meaning no hearing downtime for the patient, the company said.

Previously, patients and

Philips launches computational path software

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oyal Philips has launched a new version of TissueMark, an AI-driven application to address most critical primary tumours encountered for

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surgeons had to contend with the strong magnetic field from MRI machines exerting force on the magnet, causing torque and subsequent pain if the magnet remained in situ, even with head bandaging.

Therefore, it was common to remove the magnet for high resolution MRI examinations, requiring outpatient surgery and interrupting the patientâ&#x20AC;&#x2122;s

molecular research testing. It now supports region-of-interest detection for the majority of molecular testing and helps research labs improve the accuracy of tumour estimation.

The new version leverages deep learning AI to aid in prostate and ovarian tumour tissue identification.

The updated TissueMark

hearing during the healing process.

Advanced Bionics is developing hearing solutions for individuals with severe-toprofound hearing loss who no longer benefit from hearing aids.

software now provides tumour sufficiency guidance for lung histology, lung cytology, colon and breast tissue samples in 60 seconds in addition to guidance to whole slide images (WSI) of adenocarcinoma prostate tissue and high-grade serous carcinoma ovarian tissue.

Using a microscope for tumour estimation is subjective and leads to high variability amongst pathologists, according to Philips. By digitizing the tissue slide and analysing the image with computational software and intelligent algorithms, it can better support pathologistsâ&#x20AC;&#x2122; workflows and help labs enhance quality and reliability, while reducing costs by limiting the number of molecular tests performed with insufficient tumour content.

AI-powered solutions also have great potential to make solutions adaptive to the needs of clinicians to help

them further improve patient outcomes.

Baxter's new bone graft gets US nod

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he US FDA has granted approval for the Actifuse Flow Bone Graft Substitute for use in a variety of orthopaedic surgical procedures, said Baxter International Inc. Actifuse Flow offers accelerated bone growth in a new, easy-to-use, prepackaged delivery syringe for precise placement into small bony voids or gaps in the skeletal system. It comes ready to use with no mixing or preparation involved and maintains its flowable consistency throughout surgery.

The bone graft substitute is delivered directly from a preloaded syringe with the ability to start and stop delivery, making it compatible with open and less invasive surgical techniques and well-suited for filling small bone defects and complex geometries. As the graft substitute resorbs, it is replaced by the patientâ&#x20AC;&#x2122;s own bone during the bodyâ&#x20AC;&#x2122;s healing process.

Actifuse Flow is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bone structure. It is indicated to be packed gently into bony voids or gaps of the

skeletal system, i.e., extremities, pelvis, and spine, including use in posterolateral spinal fusion procedures with appropriate stabilizing hardware. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.

Baxter expects it to be used in a variety of orthopaedic surgeries in the pelvis, extremities, and posterolateral spine.

NephroPlus launches buttonhole needles

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ephroPlus, a network of dialysis centres in India, has introduced the buttonhole needles for painless dialysis.

Buttonhole cannulation is a technique used often in home hemodialysis where blunt needles are used instead of sharp ones.

Most dialysis patients report pain during the insertion of the needles as their biggest fear in a dialysis treatment. The Buttonhole needles addresses this issue by reducing the amount of pain drastically, according to a release.

In this technique, first a tract is formed in the flesh by pricking a sharp needle at the same point at the same angle during five to six successive dialysis sessions.

Subsequently, a blunt needle is used for cannulation that goes through this tract without

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Apple Watch Series 4 to track ECG

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he US Food and Drug Administration has cleared the Apple Watch Series 4 to operate as an OTC device to monitor ECG. The FDA approval makes Apple Watch the first device available to consumers over the counter to monitor ECG. The new Apple Watch Series 4 version has electrodes placed in the sapphire crystal and digital crown that allows users to take an ECG at any time using the app provided. The Apple Watch can show its first ECG to users without a doctor review.

The Health app allows all ECG recordings stored in so that they can be shared with healthcare professionals at a later time.

Apple plans to add more capabilities in the device later this year to aid detect atrial fibrillation.

Health-care products on ubiquitous devices, like smart watches, may help users seek treatment earlier and will empower them

with more information about their health, the FDA Commissioner Scott Gottlieb said in a statement. "The FDA worked closely with the company as they developed and tested these software products, which may help millions of users identify health concerns more quickly," he added.

The Apple Watch Series 4 line starts at $399. It is $70 more than the starting price of last year's model.

much pain. Buttonhole needle method is not only pain free; it is safer and easier for dialysis patients. Patients undergoing dialysis through this method have reported reduction of pain more than 95 per cent compared with the previous method.

NephroPlus has 128 centres currently in 82 cities across 18 states in India.

Novaerus launches plasma air purifier in India

Kleresca launches new biophotonic treatment

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N

ovaerus, an Irish company specializing in non-chemical air disinfection, launched the Defend 1050 in India.

Defend 1050 is a portable, easy to use device for rapid disinfection and purification of the air in large spaces and high-risk situations such as operating-theatres, ICUs, IVF labs, emergency and waiting rooms, and construction zones.

Defend 1050 uses patented dielectric-barrier discharge (DBD) ultra-low energy plasma technology. It utilises specifically designed multi-stage pre-filters, HEFA filters and carbon filter systems to reduce infection, absorb odours, neutralize volatile organic compounds (VOCs), and trap particulate as small as 0.3µm.

“With time, we have seen a high contamination rate in the air, which is resulting toin an alarming increase in airborne diseases and causing adverse results to human health. The plasma technology

leresca has released a new biophotonic technology for the treatment of rosacea.

The treatment uses fluorescent light energy to stimulate the skin’s own repair mechanisms through photobiomodulation.

The system consists of a patented, multi-LED Kleresca lamp designed with specific, pre-programmed wavelength settings and a specially formulated photoconverter gel. Chromophores in the gel convert light waves from the lamp into dynamic, pulsing fluorescent energy that stimulates the skin’s own repair mechanisms. The treatment is non-invasive and generally perceived as comfortable even to rosacea patients with enhanced skin sensitivity.

brought by Novaerus has been studied by NASA that has shown how the technology is an answer to this crisis,” said Una Ni Raghallaigh, Business Development Director, EMEAA region for Novaerus Inc while launching Defend 1050 at ISAR (Indian Society for Assisted Reproduction) conference organized in Aurangabad, recently.

Roche's diagnostic test for NSCLC

T

he US FDA has approved Roche’s cobas EGFR Mutation Test v2 as a companion diagnostic test (CDx) with gefitinib (Iressa).

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The treatment for rosacea is now available to patients through aesthetic clinics across 10 markets including Denmark, UK, France, Spain, Italy, Germany, Belgium, Norway, Australia and Switzerland.

Apart from reducing inflammation, the in-clinic treatment lowers the presence of papules and pustules; cuts down erythema and blushing by improving microvascularisation; mitigates the overall stress level of the skin, thereby reducing the feeling of burning and stinging and induces a healing response.

The Kleresca biophotonic system has been available on the market since 2014. The company recently obtained own CE-mark on all its products.

Gefitinib is a targeted monotherapy for the treatment of patients with advanced or metastatic epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutation-positive NSCLC. Iressa acts by inhibiting the tyrosine kinase enzyme in the EGFR, thus inhibiting the transmission of signals involved in the growth and spread of tumours.

A CDx test provides information that is essential for the safe and effective use of a corresponding therapeutic product. Clinical studies have demonstrated that patients diagnosed with NSCLC who test positive for defined mutations of EGFR gene benefit from tyrosine kinase inhibitor (TKI) therapies.

The cobas EGFR Mutation Test v2 is currently the only FDA-approved diagnostic test for NSCLC using liquid biopsy.

EGFR testing in plasma offers a non-invasive option for patients using a simple blood draw for those who are not eligible for a tissue biopsy.

The cobas EGFR Mutation Test v2 is a real-time polymerase chain reaction (PCR) test for the qualitative detection of 42 defined mutations of the EGFR gene in exons 18-21, including L858R, exon 19 deletions, and T790M mutations.

Clinical studies such as AURA, AURA2, FLAURA, ENSURE, EURTAC, and FASTACT2, have demonstrated the reliability of the cobas EGFR Mutation Test v2, Roche said.

Non-surgical option for hearing loss

M

ed-El has been granted marketing approval for Adhear, a non-surgical bone conduction hearing technology.

Adhear offers an option for people with conductive hearing loss who are not candidates for, or who would not like to undergo, bone conduction implant surgery.

It is also a treatment option for candidates with singlesided deafness and normal hearing on the contralateral side.

Adhear is easy to use. An adhesive adapter is placed onto the skin behind the ear and is worn for three to seven days at a time. The lightweight audio processor is simply clicked on and off each day. The audio processor picks up sound waves, converts them into vibrations and transmits them onto the bone via the adhesive adaptor.

The bone then transfers the vibrations through the skull to the inner ear where they are processed as normal sound.

Bone conduction uses the bones of the skull to transmit sound waves directly to the inner ear and may be an appropriate option for people who have hearing loss due to problems with the eardrum,

ear canal or middle ear.

Unlike available nonsurgical bone conduction devices that cause discomfort for the user, Adhear comfortably stays in position without applying pressure onto the skin, while its discreet location behind the ear makes it cosmetically appealing.

Med-El acquired the device’s technology from Swedish medical device company Otorix in 2016 and further developed Adhear at Med-El’s headquarters in Innsbruck, Austria.

Conductive hearing loss is caused by problems with the ear canal, ear drum, or middle ear and its tiny bones. Causes of conductive hearing loss include congenital absence of the ear canal or failure of the ear canal to be open at birth, and congenital absence,

malformation, or dysfunction of the middle ear structures.

AI algorithm to detect wrist fractures

I

magen’s OsteoDetect, a type of computer-aided detection and diagnosis software designed to detect wrist fractures in adult patients, will soon be available in the US market.

The Osteo Detect software is a computer-aided detection and diagnostic software that uses an artificial intelligence algorithm to analyse twodimensional X-ray images for signs of distal radius fracture, a common type of wrist fracture. The software marks the location of the fracture on the image to aid the provider in detection and diagnosis.

Osteo Detect analyses wrist radiographs using machine learning techniques to identify and highlight regions of distal radius fracture during the review of posterior-anterior and mediallateral X-ray images of adult wrists.

OsteoDetect can be used by clinicians in various settings, including primary care, emergency medicine, urgent care and specialty care, such as orthopedics.

It is an adjunct tool and is not intended to replace a clinician’s review of the radiograph or his or her

clinical judgement.

Imagen submitted a retrospective study of 1,000 radiograph images that assessed the independent performance of the image analysis algorithm for detecting wrist fractures and the accuracy of the fracture localisation of OsteoDetect against the performance of three board-certified orthopedic hand surgeons.

Imagen also submitted a retrospective study of 24 providers who reviewed 200 patient cases. Both studies demonstrated that the readers’ performance in detecting wrist fractures was improved using the software, including increased sensitivity, specificity, positive and negative predictive values, when aided by OsteoDetect, as compared with their unaided performance according to standard clinical practice.

Deep TMS system to treat OCD

B

rainsWay Ltd has received clearance from the US FDA for its deep transcranial magnetic stimulation (Deep TMS) system for the treatment of obsessive-compulsive disorder (OCD) in adults.

Deep TMS system is the first non-invasive medical device for the treatment of OCD. The system was granted approval in 2013 for the treatment of treatment-resistant major depressive disorder (MDD).

BrainsWay’s Deep TMS technology differs from that of other focal TMS devices as it can directly stimulate areas of the brain at a greater depth and breadth. The device can target previously unreachable areas of the brain with its H7-coil, allowing it to effectively treat OCD as well. Clinics that have a Deep TMS systems can now treat MDD and OCD patients, the company said.

OCTOBER 2018 / FUTURE MEDICINE / 85

ADVERTORIAL

Cerebrotech Visor VOLUMETRIC IMPEDANCE PHASE SHIFT SPECTROSCOPY (VIPS) DETECTS STROKE IN 30 SECONDS The Cerebrotech Visor, a new deviceworn like a visor, can detect emergentlarge-vessel occlusion in patients withsuspected stroke with 92 percent accuracy,report clinical investigators at the MedicalUniversity of South Carolina (MUSC),Mount Sinai, the University of TennesseeHealth Sciences Center and elsewherein an article published in the Journal ofNeurointerventional Surgery.

The volumetric impedance phase shiftspectroscopy (VIPS) device works bysending low-energy radio waves throughthe brain that change frequency whenpassing through fluids. Such waves arereflected back through the brain and thendetected by the device. When a patient ishaving a severe stroke, the brain’s fluidswill change, producing an asymmetryin the radio waves detected by the VIPSdevice. The greater the asymmetry, themore severe the stroke.

The Cerebrotech Visor is a noninvasivewireless device for assessing brain fluiddistribution. The Visor uses low-powerradio waves to detect bioimpedanceasymmetry, including asymmetryassociated with large acute ischemicstroke in patients undergoing neurologicassessment. In recent clinical studies,the Visor has been able to differentiatelarge strokes from small strokes with anaccuracy over 90%, a study found.

In the study, the VIPS device wasdeployed with emergency medicalpersonnel in regions served by fiveComprehensive Stroke Centres equippedwith the endovascular capabilities totreat large-vessel occlusions that underliesevere stroke.

Their goal was to use thedevice to accurately identify severe strokeand then compare the results to establishedphysical examination

methods practicedby emergency personnel such as thePrehospital Acute Stroke Severity Scale.

Both healthy participants and patientswith suspected stroke were evaluatedby emergency personnel using the VIPSdevice. Three readings were taken andaveraged—a process that takes about 30seconds. Patients were also later evaluatedby neurologists who provided definitivediagnoses using neuroimaging.

Compared to the neurologists’ diagnoses,the device displayed 92 percentspecificity—the ability to detect thedifference between patients with severestroke and those with other conditionssuch as mild stroke or healthy participantswith no brain pathology.

This places theVIPS device above standard physicalexamination tools used by emergencypersonnel that display specificity scoresbetween 40 and 89 percent.

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

86 / FUTURE MEDICINE / OCTOBER 2018

ADVERTORIAL

WebCardio – Multiday, Disposable, Wireless Holter Monitoring Solution for ECG THE NEXT GENERATION OF AMBULATORY ECG MONITORING WebCardio is a Wireless, Disposable, Multiday Holter monitor that can continuously record ECG up to three days. It can be used for detection and quantification of Cardiac Arrhythmias including Tachycardia, Bradycardia, Pauses, Conduction delays and blocks, Ventricular and Supraventricular beats and runs, and Atrial fibrillation.

The WebCardio solution developed

by GadgEon using LifeSignals’ USFDA cleared Biosensor Platform, has gone through clinical validation and commercially launched in selected cities.

The WebCardio solution consists of a body worn disposable ECG patch, a companion mobile App and cloud based Rhythm interpretation and report generation service. The nurse or technician can view the ECG waveform after affixing the ECG patch on the patient, by wirelessly pairing it with a companion mobile App. This helps technician to ascertain the quality of ECG before starting the Holter recording process. Once recording is initiated, the patient can go home and continue with their normal activities. The ECG Patch shall continuously acquire and store the data in its memory. The stored ECG data

is automatically transferred wirelessly to the already paired mobile app at a periodic interval. This data is then pushed to the cloud server from the Mobile App, when cellular network is available.

The patch can be worn by the patient up to 72 hours as prescribed by the doctor.

Once the complete ECG data is available in the server, a team of qualified cardiac technicians analyzes the ECG and creates the report using USFDA approved Holter analysis software.

Reports and the full disclosure ECG are then made available online to the doctor. The report shall optionally be emailed to the clinical personnel.

The WebCardio “Pay per Use model” allows smaller clinics and individual doctors to add Holter monitoring to their practice without any capital investment.

For the hospitals, that already has Holter recorder, WebCardio solution would help to augment the capacity without any additional capital investment and also helps to provide extended Holter monitoring service of up to 72 hours.

WebCardio solution improves the productivity and reduces the workload of

hospital personnel (nurse, technician) as ECG patch can be easily administered on a patient compared to a traditional multiple lead Holter recorders. Further, the analysis and report generation is available as service from WebCardio. The small size and compact design of ECG patch helps the patient to continue with normal daily activity, resulting in improving the diagnostic yield with better compliance and long-term monitoring. The cloud based wireless solution of WebCardio also helps the patient by reducing the hassles and costs related to multiple visits to hospital.

WebCardio will soon add more features to evolve into a comprehensive Remote patient monitoring solution including near real time monitoring services and support for multiple vital parameters. It will also have variants to support various inhospital use cases. With Machine learning and AI capabilities integrated, WebCardio will deliver advanced diagnostic decision support system, which enables predictive and proactive healthcare services. Riding on the current mobile revolution, WebCardio also helps to meet telemedicine needs to rural segment.

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

88 / FUTURE MEDICINE / OCTOBER 2018

events

debate

ISGE-Pune kicks off debate over open vs telescopic surgery Experts debate the shift from vaginal to endoscopic surgeries to find the optimal approach for patients

T

he three-day regional meeting of International Society of Gynaecology Endoscopy (ISGE) in Pune shined the spotlight on one of the most critical discussions in the field: Should new generation gynaecology surgeons restrict themselves to telescopic procedures or also look at the benefits of a complementary approach involving traditional surgeries? The debate came up in the wake of the increasing trend of promoting endoscopic surgeries in India despite the fact that both procedures have their merits and demerits as far as patient safety is concerned.

The conference, which had several theoretical lectures presented by renowned speakers in the field of gynaecological endoscopy, was also

90 / FUTURE MEDICINE / OCTOBER 2018

Doctors should not get carried away by technology campaigns and blindly say that they are exclusively laparoscopic surgeons.

Prof. Bhaskar D Goolab

Department of Obstetrics and Gynaecology, University of Witwatersrand, Johannesburg

filled with panel discussions and practical workshops on different aspects of endoscopic surgical skills and the relay of live surgeries from different parts of the world.

Though the event could successfully highlight the latest technical advances and innovations which are making surgeries safer and cost effective, a discussion over the traditional approach versus the new was an eye-opener, especially to new age clinicians.

Sharing his decades-long experience in open as well as endoscopic gynaecological surgeries in India and abroad, Prof. Bhaskar D Goolab, Department of Obstetrics and Gynaecology, University of Witwatersrand, Johannesburg, South Africa, said that there are merits

Although the cost of laparoscopic surgeries are higher compared to conventional procedures, these new methods help reduce the days of hospital stay.

Since the hospital meter starts running from the very moment the patient gets admitted, a reduced hospital stay is often a big saving for the patient.

Dr P G Paul

Senior Gynaecologist & Endoscopist

Chairman of Paul Hospital

in both procedures. But, doctors, especially new-age gynec-surgeons, should not get carried away by technology campaigns and blindly say that they are exclusively laparoscopic surgeons. These kind of conferences are there to put such issues in perspective, he added..

“There is a debate that has come up now as to what is the role of telescopic surgery and what is the role of the conventional and longtrusted open surgery. There are merits, indications and pitfalls on both sides of the equation, but the key point of contention here is the paradigm shift that is predominantly driven by technology players towards these expensive surgeries. Gynaecologists simply follow the trend of telescopic surgery, unnecessarily turning some simple traditional procedure into an expensive technology procedure instead of weighing the specificity, fit case, patient choice and safety,” Dr Goolab said.

“Of course, there is merit in suitably chosen cases. For example, diseases like endometriosis or massive uterine fibroids, which makes the removal process difficult through the vaginal route, need to be done 92 / FUTURE MEDICINE / OCTOBER 2018

Dr Rishma Dhillion Pai

through telescopic surgery, depending on the skill of the doctor. There are also risk factors like burn and other complications associated with endoscopic surgeries as it uses electric power,” he added.

While others agreed with the view that the debate remains relevant as far

We wanted to showcase the Indian skill-set in endoscopy to the world through this event and, at the same time, wanted our young gynaecologists to learn from the experienced doctors from all over the world.

Dr Sunita Tandulwadkar

Organising Chairman, ISGE-Pune

as some specific cases are concerned, they argued that laparoscopic technologies have actually made procedures much easier for the patient and the surgeon, both technically and in terms of indirect costs.

According to Dr P G Paul, one of the most senior gynaecology and endoscopic surgeons in India and the chairman of Paul Hospital, it is natural that technology development drives the industry to better options, though doctors always have the opportunity to choose the best according to his/her skill-set and the benefit of the patients.

“It is not only the procedure cost that matters in the overall treatment.

Although the cost of laparoscopic surgeries are higher compared to conventional procedures, these new methods help reduce the days of hospital stay and the patients can resume their routines faster after the surgery,” Dr Paul said.

“The advanced and innovative technologies in endoscopy have effectively helped in saving both cost and time for patients, though the cost of the procedure as such is comparatively higher. Since the hospital meter starts running from the very moment the patient gets admitted, a reduced hospital stay is often a big saving for the patient,” said Dr Rishma Dhillion Pai, Senior Gynaecologist & Endoscopist and President, Indian Association of Gynaecological Endoscopists (IAGE).

Dr Sunita Tandulwadkar, the organising chairman of the 2018 regional conference, said the conference was unique in several aspects, including the presence of live workshops, academic sessions and a number of senior national and international speakers.

“Also, we wanted to showcase the Indian skill-set in endoscopy to the world through this event and, at the same time, wanted our young gynaecologists to learn from the experienced doctors from all over the world, who shared their 25-30 years’ experience in handling unique cases,” she said.

events

KENTCON-2018 highlights advancements in otolaryngology The 3-day event stressed the need for exchanging ideas in multifarious areas of ENT practice DIVYA CHOYIKUTTY

T

he 17thannual conference of Association of Otorhinolaryngologists of India highlighted emerging technology breakthroughs and surgical techniques, such as computer assisted navigation, endoscopic skull base surgery and facial reanimation.

KENTCON-18, which was held from 7th to 9th September in Kochi, was attended by over 500 otorhinolaryngologists from across the globe. The three-day convention, organized by the Kerala State Branch of AOI in association with Cochin Society of Otorhinolaryngologists for Medical Society (CSOM), stressed the need for exchanging ideas and creating awareness on medical technologies and advancements in multifarious areas of ENT. Dr. Preethy Mary from Medical Trust Hospital, Cochin said the new concepts in endoscopic surgery are helping with the removal of tumours from inaccessible locations of skull base.

“Some of the tumours located at extremely inaccessible locations like the skull base can now be removed through the nasal route via endoscopy,” she said.

“Earlier, the removal of such tumours of the pituitary gland was entirely a domain of neurosurgery. The new techniques in nasal endoscopy now make it possible to remove these difficult-to-access tumours as a combined procedure of transnasal pituitary surgery,” Dr Mary added.

The diagnosis of ENT disorders too have improved with the advent of technological advancements involving endoscopy, ultrasonography,

94 / FUTURE MEDICINE / OCTOBER 2018

The refinement of ultrasound technology for noninvasive localisation of airway obstruction helps proper clinical validation and early diagnosis of OSA. Dr. Amal Isiah

University of Maryland

implants and surgical navigation, which has helped in implementing better treatment and minimizing the number of complications and hospital stays.

The conference also featured a live surgical demonstration of facial reanimation on cadaver, performed

by Dr. Kalpesh Vakharia, to highlight the management of facial paralysis, one of the most complex areas of

reconstructive surgery.

Significant advances in the field of trans-oral robotic surgery (TORS) and the minimal invasive approach towards efficient resection of tumours in the oropharynx area were elucidated by Dr. Kyle M. Hatten, who also reflected on the slow, but steady rise in oropharyngeal cancer seen over the past decades.

He also mentioned the risk of human papilloma virus, which is expected to be the major causative organism for head and neck cancer in the US by 2030.

Stressing the importance of managing obstructive sleep apnea (OSA), Dr. Amal Isiah of University of Maryland, said: ”The refinement of ultrasound technology for noninvasive localisation of airway obstruction along with the conventional technique of polysomnography, helps proper clinical validation and early diagnosis of the disorder.”

The conference also cautioned about the lack of new research in the field, and that the country has always been dependent on technologies invented and patented elsewhere.

Several experts from across India and GCC participated in the conference.

NEXTGEN GENOMICS, BIOLOGY, BIOINFORMATICS AND TECHNOLOGIES CONFERENCE SEP 30 th - OCT 2 nd , 2018

FAIRMONT, JAIPUR, INDIA

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

is an international meeting organized by SciGenom Research Foundation (SGRF), a not-for-proďŹ t organization working to promote Science, Research & Education. The conference will also focus on convergence of clinical and genomic technologies for better healthcare outcomes.

Key topics include: Clinical genomics Cell free DNA Exome Sequencing Genome sequencing Human genomics Liquid Biopsy Medical Genomics Non-Invasive testing Onco-Genomics Pharmacogenomics Protein engineering Protein structure RNA-Seq Sequencing SNP Analysis Whole Genome Sequencin

20 keynote lectures; 50+ talks 1000 delegates; 200+ posters Vendor Exhibition

Live and Let Live: Snakebite Cure Symposia

Oct 1st 2018, Jaipur, India

Genomics Project Grants Student Meeting Scholarships Travel Awards Co-hosts

Sponsors

Ms. Lakshmi V | M: +91-9591506568 / Mr. Srijith VM | M: +91- 9497118365 ngbt2018@sgrf.org | www.sgrfconferences.org | www.sgrf.org

Knowledge Partner & Poster prize sponsors

Media Partners

calendar

Upcoming conferences OCTOBER SURGERY OF THE HAND

5- 7 42nd Annual Conference of Indian Society for Surgery of the Hand (ISSHCON) Coimbatore, Tamil Nadu ORTHOPAEDICS

Conference of Indian Arthroscopy Society (IASCON) Kozhikode, Kerala 6-7 SURGERY

Asian Conference of Tumor Ablation Chennai, Tamil Nadu

ANAESTHESIA

25 - 27 International Diabetes Federation (IDF) Diabetes Complications Congress 2018 Hyderabad, Telangana UROLOGY

Zone Conference of Urological Society of India-West Zone (ZCUSI) Raipur P E D I AT R I C S

26-28

P E D I AT R I C DIABETES

11 - 14

44th Annual Conference of International Society for Pediatric and Adolescent Diabetes (ISPAD) Hyderabad, Telangana

ICRAMHS

15-16 Academics World 470th Intl Conference on Recent Advances in Medical and Health Sciences New Delhi

SLEEP APNEA

10-11 AOCMF Seminar Advances in Sleep Apnea and Orthognathic Chennai, Tamil Nadu 14-16

29-30 IASTEM -485th International Conference on Medical, Biological and Pharmaceutical Sciences Delhi

NOVEMBER SKULL BASE SURGERY

1-3

Respiratory Drug Delivery (RDD) Asia Conference 2018 Kochi, Kerala PA E D I AT R I C NEUROLOGY

15-18 15th International Child Neurology Congress Mumbai, Maharashtra 15-18

UROLOGY

Annual Conference of Urological Society of India East Zone Chapter (ACUSIEZC) Ahmedabadt

The announced dates of the conferences may change 96 / FUTURE MEDICINE / OCTOBER 2018

Conference of Indian Society of Anaesthesiologists Agra INFECTIOUS DISEASES

28-29 World Congress on Infectious Diseases and Antibiotics Bengaluru 28-Dec 1

IPS

Annual Conference of Skull Base Surgery Society of India (SKULLBASECON) Ludhiana

25-29

GASTROENTEROLOGY

ICMBPS

NANOMEDICINE

12-14 International Conference on Nanomedicine and Tissue Engineering (ICNT) Ettumanoor

ANAESTHESIOLOGY

Telemedicon 2018 - 14th International Conference of Telemedicine Society of India Amravati, Andhra Pradesh

R E S P I R AT O R Y DRUG DELIVERY

National Conference on Pediatric Infectious Diseases (NCPID) Ahmedabad

NUCLEAR CARDIOLOGY

Annual Conference of Cardiological Society of India Mumbai

DIABETES

XENOBIOTICS

10-13 Conference of the Indian Society for the Study of Xenobiotics Bangalore, Karnataka Chennai, Tamil Nadu

TELEMEDICINE

19-21 ISACON Gujarat Surat

46th IPS National Conference Mangalore 2018 Mangalore, Karnataka NUCLEAR CARDIOLOGY

Annual Conference of Indian Society of Gastroenterology (CISG) Ernakulam GENOMICS

29-30 Next Generation Sequencing in Clinical Genomics Bengaluru OPHTHALMOLOGY

29-Dec 2 Conference of Vitreo Retinal Society Jaipur BURN INJURIES

30-Dec 4

22-25 American Society of Nuclear Cardiology (ASNC) Society of Nuclear Medicine Chandigarh, Chandigarh

19th Congress of the International Society for Burn Injuries (ISBI) Gurugram, Delhi

book review

FOETUS AS A PATIENT T

PRINCIPLES AND PRACTICE OF FETAL MEDICINE

By Raju R Sahetya, Jaideep Malhotra & Hema Purandarey pp381 Jaypee Brothers

he prevalence of genetic diseases and birth defects in India is far higher than what is apparent on casual observation. Advances in genomics and growing awareness would certainly help to fathom the situation better. Still, since genetic disorders are multisystem and lifelong, genetic services alone won’t entirely suffice. The efforts should be integrated with related medical services like prenatal health, preconception planning, child development monitoring etc..

This is where the emerging discipline of Foetal Medicine achieves greater importance.

The scope of prenatal diagnosis, through the last four decades, has increased from routine to predictive diagnosis of disorders that are likely manifest later in life.

Principles and Practice of Fetal Medicine, authored by Raju R Sahetya, Jaideep Malhotra and Hema Purandarey, presents an extensive discussion of the rapidly expanding field of prenatal and perinatal diagnosis and treatment.

Spread across forty-three chapters covering every aspect of foetal medicine, the book forms a major source of reference and guidance to a wide range of professionals.

Starting with an overview of prenatal diagnosis, the ten sections of the book give in-depth insights into prenatal counselling, invasive and non-invasive prenatal screening and diagnostic techniques, lab techniques on genetic testing and pre-implantation diagnosis, antenatal use of foetal therapy, prenatal foetal surgery, ethical and medicolegal aspects and the future of prenatal diagnosis.

The concluding section of the book offers good practice guidelines recommended by the International Federation of Gynaecology and Obstetrics (FIGO) and best practice

advice on maternal-foetal medicine.

These sections, coupled with more than 350 clinical photographs, tables, illustrations, figures and charts, make Principles and Practice of Fetal Medicine a ready-reckoner and a handbook of choice for obstetricians, geneticists, genetic counsellors, ultrasonologists, paediatricians and lab technicians.

The authors, after providing brief historical and contemporary perspectives, attempt to trace the influence of genomic

EMPHASISING THE NEED FOR AN ”ENERGETIC SHIFT” IN THE RESEARCH FOCUS ON PRENATAL SCREENING AND DIAGNOSIS, THEY CALL FOR AN EXPANSION OF ALL FUTURE STUDIES TO INCLUDE THERAPEUTIC STRATEGIES.

medicine in pregnancy management and pregnancy outcome in coming days.

Emphasising the need for an ”energetic shift” in the research focus on prenatal screening and diagnosis, they call for an expansion of all future studies to include therapeutic strategies.

Although the ultimate objective of the book is to promote improved clinical management of pregnancies affected by an anomalous foetus, the immediate goals include better detection, diagnosis and understanding of ”the Foetal Medicine and foetus as a patient”, as the authors state in the preface.

OCTOBER 2018 / FUTURE MEDICINE / 97

FAILURE TO VIEW PATIENT AS A WHOLE IS A HUGE TRAGEDY DR M R RAJGOPAL Founder, Pain and Palliative Care Society, Kozhikode

I

was trained as an anaesthesiologist in the early part of my career, when the responsibility of giving relief from pain was gradually coming into our field. In Calicut (now Kozhikode), where I first began working at a senior level, I was doing nerve blocks on various parts of the body.

However, an experience with one patient in the 1980s compelled me to take a fresh look at what I was doing. This was a 42-year old college professor, suffering from cancer, and he was referred to me for pain relief. I did for him what I had done for numerous others and his pain receded but a day later, he committed suicide! Everyone in my department was shocked because here was a case where our treatment was a success, and yet we lost the patient.

On enquiry, I was told that he had been given the impression that my treatment was intended to cure his cancer. Nobody had made it clear that it was for the limited purpose of relieving the severe pain that he was suffering from. When he realized that his cancer was essentially incurable, he gave up all hope of life itself.

It conveyed to me the invaluable lesson that every doctor must look at his patient as a whole person, and not just a collection of organ systems. It is a mistake that many doctors make even today – they treat the 98 / FUTURE MEDICINE / OCTOBER 2018

disease, and not the person suffering from a disease.

For me as an individual, it brought me face to face with my calling – to develop the (then) nascent field of palliative care. My colleagues and I work through an organization named Pain and Palliative Care Society, based in Kozhikode. Set up in 1993, it is able to reach out to patients wherever they are. Thus, we have managed to cater to over 3 million patients till now.

Our experience has lessons for doctors and healthcare professionals in other countries as well, because of which we have worked with the WHO Collaborating Centre of the Pain and Policy Studies Group (PPSG) from a very early stage. Here, the purpose was to bring about changes in the regulatory policy with regard to opioids and other pain-relief medicines. In a situation of terminal illness, we can take the risk of the patient developing an addiction, if it means improving the quality of life for the patient in the final stages. In such cases, the priority becomes different from the usual.

The huge tragedy of healthcare today is that, because it fails to view the patient as a whole, the doctors inflict suffering in the process of treating a disease! ­— As told to Dr Sumit Ghoshal

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