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MALAYSIA

1-31 January 2015

IBD on the rise in Asia, most cases


reported in China
Malaysia Focus
Advancement in oxygen
therapy

Conference
Coverage
Challenges in the
management of acute
severe ulcerative colitis

International
Air pollution a leading
preventable cause of
death worldwide

1 -31 Ja n ua ry 2 01 5

IBD on the rise in Asia, most cases


reported in China
Elvira Manzano

here has been a progressive increase in the


incidence and prevalence of inflammatory

bowel disease (IBD) in Asia, characterized by


complicated disease behavior and significant
morbidity, says an expert at the recent Asian
Pacific Digestive Week conference held in Bali,
Indonesia.
IBD has been traditionally known as a disease of the West and is relatively rare in Asia.
However, time trend studies from Japan, Ko-

penetrating or stricturing] was more common in

rea and Hong Kong have collectively shown a

Asia than in the West, said Ng.

two-to-three fold increase in the incidence and

In Hong Kong, for example, a study showed

prevalence of IBD in the past 10 years, said

the rate of perianal disease was 29.2 per-

Professor Siew Chien Ng of the department of

cent compared with 15.8 percent in Austra-

medicine and therapeutics, Chinese University

lia (p=0.001). [J Gastroenterol Hepatol 2012;

of Hong Kong in Hong Kong.

27:1266-80]

In the first large scale population-based

These changes may have been due to our

study of IBD involving seven countries in Asia

increased contact with the West, westernization

(China, Hong Kong, Macau, Thailand, Malay-

of diet, improved hygiene, increasing antibiotic

sia, Singapore, Sri Lanka) and Australia, the

use, immune dysregulation and changes in the

incidence of IBD varied from 0.54 to 3.44 per

gut microbiota, Ng said. Asian patients with

100,000 individuals. China had the highest in-

CD have altered microbiota compared with their

cidence of IBD at 3.44 per 100,000. Ulcerative

Caucasian counterparts. Mucosa-associated

colitis (UC) was more prevalent than Crohns

microbiota in IBD may also differ geographi-

disease (CD), although the incidence of CD

cally.

was rapidly increasing in certain areas. [Gastroenterol 2013;145:158-65]

In a more recent population-based casecontrol study in Asia, where Ng was the prin-

Although family history of IBD was less

cipal investigator, breastfeeding, having pets

common in Asia as were extra-intestinal mani-

and better sanitary conditions were shown to

festations complicated CD [perianal disease,

be protective of IBD, suggesting that child-

1 -31 Ja n ua ry 2 01 5

hood environment plays an important role

sians, which may impact the development of

in modulating disease development. [Gut

IBD, added Ng. NOD2 and autophagy variants

2014; pii: gutjnl-2014-307410. doi: 10.1136/

(ATG 16L1 and IL 23) are not associated with

gutjnl-2014-307410]

CD in Asians, but TNF-SF15 polymorphisms

The results, Ng said, highlight the impor-

are strongly associated with CD.

tance of childhood immunological, hygiene and

Understanding of the genetic variation and

dietary factors in the pathogenesis of IBD, sug-

mutations [of IBD] will help us to identify bio-

gesting that markers of altered intestinal micro-

logical pathways causing the disease and to

biota may modulate risk of IBD later in life.

discover better drugs for patients. More studies

There are also differences in the genetic


mutations of IBD between Asians and Cauca-

are warranted to determine the critical etiologic


factors for IBD, Ng said.

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1 -31 Ja n ua ry 2 01 5

F O RUM

Universal Health Coverage in the


ASEAN Region
Universal healthcare coverage has been on everyones minds since the proposal
of Malaysias very own version - the 1Care. Nathorn Chaiyakunapruk, professor of
health economics, School of Pharmacy, Monash University Malaysia, gives his views
on challenges facing its implementation.

HO describes that the goal of Universal

sal Health Coverage. This includes financial

Health Coverage is to ensure everyone

constraints due to low levels of government

obtains the health services they need without

funding; insufficient health workforces and un-

suffering financial hardships when paying for

equal distribution of health professionals; and

them. It is thus a critical component of sustain-

increasing burdens of non-communicable dis-

able development and poverty reduction; and

eases (NCD), persisting infectious diseases,

a key element to reduce social inequities.

and reemerging pandemic infectious diseases.

In comparison to her ASEAN neighbors,

With the ASEAN Economic Community

Malaysia is doing very well, especially with re-

(AEC) setting a goal of regional economic in-

gards to incidence of catastrophic medical ex-

tegration by 2015, ASEAN leaders have identi-

penditures. However, the country should look

fied healthcare as a priority sector. The open-

at improving the quality and services at public

ing of healthcare markets promises substantial

hospitals, in order to reduce out-of-pocket ex-

economic gains but intensifies existing chal-

penditures.

lenges to promote equitable access to health-

He further elaborated that the score of 35.6

care within countries. The services sector inte-

percent in out-of-pocket, of total health expen-

gration goals of the AEC present the biggest

diture in 2012, is still considered high. This

challenges as well as biggest opportunities for

would place Malaysians at risk financially, indi-

the region.

vidually as well as in terms of household.

Some countries such as Singapore and

In a recent paper Progress towards Uni-

Thailand have already become significant ex-

versal Health Coverage in ASEAN written to-

porters of modern services in sectors such

gether by a team of researchers representing

as professional services and information and

Cambodia, Indonesia, Laos, Malaysia, Myan-

communication technology (ICT), including

mar, Philippines, Singapore, Thailand and Viet-

business processing outsourcing (BPO), high-

nam, it is reported that ASEAN countries face

er education, and health tourism. Some coun-

several common barriers in achieving Univer-

tries face challenges related to the opening of

1 -31 Ja n ua ry 2 01 5

F O RUM

healthcare markets. For example, despite the

sustainable and equitable financing; select-

golden opportunity to tap into the large mar-

ing the right benefit package; and reorganis-

ket of the Indonesian population, multinational

ing domestic health expenditures to be used

healthcare companies had shown lukewarm

more efficiently. For ASEAN countries, UHC

responses to invest in Indonesia due to the

can be explicitly considered to mitigate dam-

restrictions and regulations on foreign invest-

aging effects of economic integration. Political

ments in the country.

commitments to safeguard health budgets and

Progressive liberalization of services of

increase health spending will be necessary

health professionals also poses risks to health

given liberalizations risks to health equity as

equity within and between countries. Accord-

well as migration and population aging which

ing to the Mutual Recognition Arrangement

will increase demand on health systems.

(MRA) of the AEC, physicians, nurses, and

It is definite that ASEAN countries face im-

dentists are among seven selected profession-

mense challenges when it comes to ensuring

al groups that are free to work across member

UHC. However with aligned regional policies

countries. Although the financial returns from

and increased investment in public health

this strategy seem substantial, issues of equity

systems, the outlook is positive as the region

within UHC have become a concern due to the

shows potential to become a force to be reck-

possibility of health worker flight from poorer

oned with on championing better health. Hope-

regions already struggling to ensure UHC.

fully this will result in higher health and safety

On a brighter note, UHC can be achieved

standards, comprehensive social protection,

even among low and middle-income countries

and improved health status of the ASEAN pop-

by strengthening the health system; securing

ulation.

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1 -31 Ja n ua ry 2 01 5

ME DI C A L B R I E F S

Compounded medicine center at CGH

new center at Changi General Hospital will

ic region, proposes to innovate in two key areas.

provide personalized medications, normally

First, it hopes to create a seamless, integrated

received only in a hospital, to patients at home.

system for creating and delivering customized

Some drug preparations need to be custom-

medications from the point that doctors give pre-

ized according to a patients body weight, kid-

scriptions to nursing support at home and follow

ney or liver function, or according to form, if, for

up care.

example, a powder preparation needs to be reconstituted.

Second, better clinical protocols could increase the number of patients that can be safely

Delivering these customized, or compound-

and effectively cared for with Compounded Ster-

ed, products to patients at home is the focus of

ile Products (CSPs) in their own homes those

the new Centre of Excellence in Compounding

who require intravenous antibiotics, for exam-

Science at CGH, together with Baxter Health-

ple, and sometimes need to stay in a hospital

care (Asia) Pte Ltd.

for over a month, or outpatients who still need

By enabling customized medication to be


ordered, compounded, delivered and administered safely and conveniently to patients at
home, we are making it possible to bring more

to commute to their hospital nearly every day for


proper drug delivery.
These processes could also benefit patients
in nursing homes or community hospitals.

treatment modalities out of the hospital and into

Completion of the S$8 million center is ex-

the community, said CGH CEO Dr. Lee Chien

pected in 2017. An Academy of Compounding

Earn.

Sciences run by Baxter is also in the works to

The center, the first of its kind in the Asia Pacif-

bolster expertise in CSPs.

1 -31 Ja n ua ry 2 01 5

ME DI C A L B R I E F S

Many childhood vaccines safe

study shows that two measles-containing

same-day measles-mumps-rubella and varicella

vaccines are safe for young children and

(MMR+V) vaccine. After vaccination, they did

do not increase their risk for seven major neu-

not have an elevated risk for immune thrombo-

rological, hematological and immune system

cytopenia purpura (ITP), anaphylaxis, ataxia, ar-

disorders.

thritis, meningitis or encephalitis, acute dissemi-

The findings should reassure the public that

nated encephalomyelitis and Kawasaki disease.

adverse effects of measles-containing vaccines

In children aged one, MMRV and MMR+V

are very rare, and parents with one-year-olds

were linked to fever and febrile seizure 7 to 10

can opt for MMR+V instead of MMRV vaccines

days post-vaccination. Compared to MMR+V,

to lower the risk, said lead author Dr. Nicola P.

MMRV is associated with a higher risk of sei-

Klein (Ph.D), codirector of the Kaiser Perman-

zures in children at that age. Nevertheless, the

ente Vaccine Study Center, US.

risk is only less than one febrile seizure per 1,000

Children who participated in the 12-year

injections. Previous studies found no increase in

study were given either measles-mumps-rubel-

risk for fever or febrile seizure post-vaccination

la-varicella (MMRV) or separately administered,

among children aged 4 to 6 years.

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1 -31 Ja n ua ry 2 01 5

M A L AYS I A foc u s

10

Diabetes Asia 2014 Conference, October 16-19, Kuala Lumpur, Malaysia.

Making dialysis provision more


sustainable
Dr. Joslyn Ngu

s the incidence of diabetes continues to


rise, so too will renal failure and the need

for dialysis. With that scenario in mind, a more


sustainable healthcare system will be required
to ensure Malaysia can cater to the surge in demand for dialysis services, says a specialist.
Some ways to improve the sustainability of
dialysis provision are by encouraging prevention programs, improving pre-dialysis patient
education, promoting low cost hemodialysis,
advocating home based therapies and advanc-

We have to focus on bringing dialysis patients back to


work in order to make allow them to be productive again

ing rehabilitation and back-to-work schemes,


said consultant nephrologist Dr. Thiruventhiran

sis, only SOCSO has a policy in place for dialy-

Thilaganathan.

sis patients to return to work. Most of the other

According to the National Kidney Foundations 2013 statistics, only 14.5 percent of di-

payers classify end stage renal disease (ESRD)


as a total disability.

alysis patients were working. Additionally, the

Even though the cost of dialysis has in-

majority who worked earned less than RM1,000

creased from RM110 per treatment in 2006 to

per month, said Thiruventhiran. Emphasizing

RM140 per treatment in 2013, the government

the importance of rehabilitation for dialysis pa-

subsidy has not increased, said Thiruventhiran.

tients, he said that if patients are able to hold

Hence, besides escalating efforts to rehabilitate

a job, they can contribute to the economy and

patients, alternatives such as peritoneal dialysis

pay taxes. Part of tax money is channeled into

or low cost hemodialysis need to be promoted

healthcare, so this will aid the cause of forming

to further increase the sustainability of dialysis

a sustainable healthcare system in the country.

provision. The Private Healthcare and Facili-

Currently, dialysis providers do not have an

ties Services Act should also be reviewed as it

inbuilt rehabilitation program for their patients.

seems to have increased the cost of manpower,

Also, among organizations which pay for dialy-

which has led to increased cost of dialysis ther-

1 -31 Ja n ua ry 2 01 5

MA L AYS I A foc u s

11

number of diabetics, the amount of patients re-

apy, he suggested.
Locally, the funding for dialysis services

quiring dialysis therapy will increase. At the mo-

comes from both private (ie, out-of-pocket ex-

ment, when compared to other countries, Malay-

penditure (OOPE), insurance and employer)

sia is doing well in terms of having a sustainable

and public sectors (ie, government, pension

healthcare system. However, more needs

and zakat). Dialysis places a heavy burden on

to be done to ensure it remains sustainable

the countrys economy and with the increasing

in the future.

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11/20/14

1:44 PM

1 -31 Ja n ua ry 2 01 5

M a l aysia F oc u s

12

Diabetes Asia 2014 Conference, October 16-19. Kuala Lumpur, Malaysia.

Possible impact of 1Care on dialysis


provision
Dr. Joslyn Ngu

he provision of safe and cost effective dialysis treatment for all patients, regardless of

state and sector, is expected from 1Care, says


an expert.
Dialysis treatment has become increasingly
accessible throughout the years. However, gaps

before they can work in dialysis centers, and ac-

still exist in certain aspects of dialysis provision.

creditation for dialysis centers, said Ghazali. To

Not everybody who needs dialysis therapy gets

further raise and standardize the quality of dialy-

treated, and for those who are treated, not all

sis therapy, a body might be established to reg-

will get the appropriate treatment, said Datuk Dr.

ister and monitor those who work in the field of

Ghazali Ahmad Kutty, head of the nephrology

dialysis or even the dialysis center itself, he said.

department, Kuala Lumpur Hospital.

At the moment, gaps exist in the distribution,

Currently, dialysis centers in Malaysia rely on

equity, funding and quality of dialysis treatment.

voluntary, public and private sectors for funding.

To improve the provision of dialysis in the fu-

With the introduction of 1Care, it is probable

ture, effective plans need to be implemented to

that new rules will be implemented to ensure

bridge the accessibility gap between different

smoother distribution of the funds.

regions in the country and raise the quality of

1Care is a newly restructured national health

dialysis treatment, said Ghazali.

system that is currently in the pipeline. It is cre-

Elaborating on the unequal distribution of

ated to ensure universal coverage for healthcare

healthcare resources, he said the ratio of nurses

needs based on solidarity and equity. One of

to patients in hemodialysis units differs between

its many objectives is to ensure affordable and

states, with Johor having the highest ratio and

sustainable healthcare. Another is to provide eq-

Sabah the lowest. Hemodialysis centers in Ma-

uitable, efficient, higher quality care and better

laysia are also unequally distributed with Penang

health outcomes.

having the most centers and Sabah the fewest.

Other changes to dialysis provision that

The availability of hemodialysis centers in each

might be introduced along with 1Care include

state in Malaysia does not match the number of

specific certifications for healthcare providers

patients who require treatment, he stated.

Find out what these experts have to say about how to improve
patient care for osteoporosis and sarcopenia in Asia through
awareness building and the use of new therapies

Professor
Peter Ebeling

Professor
Serge Ferrari

Dr Edith Lau

Professor Bess
Dawson-Hughes

Widespread vitamin D
deficiency and low calcium
levels in Asians

Selective estrogen
receptor modulators
(SERMs), a new class of
therapy for post-menopausal
woman with osteoporosis

Treatment plans for


post-menopausal women
with osteoporosis

How aging contributes to


sarcopenia and impaired
muscle function in the
elderly

How low levels of awareness


in the public and in
healthcare professionals
affect osteoporosis care in
Asia
Benefits of fracture
registries and fracture liaison
registries (FLS) in Asia

MIMS Video Series features

interviews with leading experts

For A 5-minute Update


Go to www.mims.asia/video_series

SCAN TO WATCH VIDEO

Brought to you by MIMS

1 -31 Ja n ua ry 2 01 5

M A L AYS I A foc u s

14

Advancement in
oxygen therapy
Dr. Joslyn Ngu

xygen therapy has been used in the medical field since World War I and is still an

important modality in patient care today.


In adults, treatment with oxygen is indicated
in conditions that cause hypoxemia, such as severe asthma attacks, severe pneumonia, chronic pulmonary obstructive disease, cystic fibrosis
and sleep apnea. [National Heart, Lung and
Blood Institute. Oxygen therapy. Available at:
http://www.nhlbi.nih.gov/health/health-topics/topics/oxt/whoneeds Accessed on 29 Dec]
In most developing countries, there are two
sources of oxygen - oxygen cylinders and oxygen concentrators. The oxygen in cylinders
undergoes liquefaction and distillation (which
produces pure oxygen), before it is kept under
pressure in cylinders. Meanwhile, oxygen concentrators work by filtering out other elements in
the air and storing oxygen exclusively.
Both oxygen cylinders and oxygen concentrators have their own advantages and disad-

apps.who.int/iris/bitstream/10665/60985/1/

vantages. Oxygen cylinders have a low capital

WHO_ARI_93.28.pdf?ua=1 Accessed on 29

cost but high running cost. They also need to be

Dec]

transported back to supply depots to be refilled.

To improve the effectiveness of oxygen ther-

On the other hand, oxygen concentrators have

apy, Linde Malaysia recently introduced an oxy-

a high capital cost but low running cost. Unlike

gen cylinder equipped with an integrated valve,

cylinders, they do not require refilling but they

which weighs less than six kg. It is the lightest

need electricity to work. [WHO. Oxygen therapy

medical oxygen cylinder available in Malaysia.

for acute respiratory infection in young children

Additionally, the integrated valve makes it easy

in developing countries. Available at: http://

to control the flow of oxygen and displays the

amount of oxygen left.

1 -31 Ja n ua ry 2 01 5

M a l aysia F oc u s

15

Oxygen therapy is also recommended for

In their recommendation for oxygen therapy,

children with conditions such as severe acute

the WHO stated that in a setting where pulse

respiratory tract infection, severe or prolonged

oximetry is not available, oxygen therapy is rec-

convulsions, severe anemia complicated by re-

ommended for neonates who have cyanosis, a

spiratory distress and shock.

respiratory rate higher than 60, or are too sick

Despite it being a much needed healthcare

to feed. If pulse oximetry is available, oxygen

modality, especially in acute care settings, some

therapy should be given to neonates with SpO2

are still skeptical regarding the cost effective-

less than 90 percent. [WHO. Informal consul-

ness of oxygen therapy. This is because oxygen

tation on clinical use of oxygen. Available at:

therapy needs to be continuously administered

http://www.who.int/surgery/collaborations/

to be effective and most developing countries

Oxygen_Meeting_Report_Geneva_2003.pdf

lack the resources ie, manpower and funding,

Accessed on 29 Dec]

for continuous oxygen therapy.

1 -31 Ja n ua ry 2 01 5

MA L AYS I A foc u s

16

Fifth cause of human malaria


emerges
Dr. Joslyn Ngu

habitat of macaques and are bitten by Anopheles mosquito, Balbir explained.

malaria parasite commonly found in long-

P. knowlesi causes only mild symptoms in

and pig-tailed macaques, Plasmodium

macaques, but in humans can cause mild to

knowlesi, is now acknowledged as the fifth spe-

severe symptoms and is potentially fatal if not

cies of Plasmodium to infect humans, an expert

treated in time. The parasite multiplies every 24

says.

hours in the blood, making it the quickest repli-

In an exclusive interview with Medical Tri-

cating malaria parasite to infect humans.

bune, Professor Balbir Singh (Ph.D), director

Under the microscope, it is hard to distin-

of the Malaria Research Center, Universiti Ma-

guish P. knowlesi from P. malariae as they have

laysia Sarawak (UNIMAS), said that some hos-

a similar morphology. Nevertheless, a differen-

pitals in East Malaysia found P. knowlesi to be

tiating feature is that P. malariae has a gener-

the cause of the majority of hospitalized ma-

ally low parasite count (<5,000 parasites/L)

laria cases. [Emerg Infect Dis 2011;17:814-20,

and hospitalization rate, whereas P. knowlesi

Med J Malaysia 2010;65:166-72, Clin Infect Dis

has a high parasitemia and hospitalization rate.

2013;56:383-97]

Diagnosis can be confirmed using nested poly-

According to research he published in 2004,

merase chain reaction (PCR) assays, but these

Balbir said 58 percent of malaria patients in a

are normally available only in specialized diag-

Kapit hospital were found to be infected with

nostic and research laboratories.

P. knowlesi. [Lancet 2004;363(9414):1017-24]

The majority of P. knowlesi malaria patients

Human cases of P. knowlesi malaria are not lim-

respond well to the usual treatment regime

ited to Malaysia and have been reported in all

of chloroquine, but if patients are vomiting or

other Southeast Asian countries except Laos.

parasite counts are high, then intravenous an-

The incidence rate in East Malaysia is much

timalarials such as artesunate should be given.

higher compared to other states and countries

The number of complicated and fatal cases is

but this could be due to the more extensive

currently on the rise. Treatment for complicated

studies done in East Malaysia.

P. knowlesi malaria infection should be based

Most P. knowlesi malaria patients in Sarawak


were those who stayed or worked in the forest

on WHOs guidelines for treating severe P. falci-

parum malaria.

ie, farmers, logging camp workers and hunters.

Among the challenges to disease preven-

Being a zoonotic disease, humans can be in-

tion is that current preventive methods are

fected by P. knowlesi only when they enter the

more focused on indoor prevention of mosqui-

1 -31 Ja n ua ry 2 01 5

MA L AYS I A foc u s

17

to bites, thus are ineffective for the prevention

There are still many questions that need

of P. knowlesi malaria which is caused by out-

to be answered regarding P. knowlesi ma-

door feeding mosquitoes. Moreover, there have

laria. While ongoing research continues to

been findings of P. knowlesi in mosquitoes that

improve understanding of this new parasite,

are vectors for P. falciparum and P. vivax, indi-

healthcare providers should keep an eye

cating that the parasite may be transmitted from

out for the disease, particularly in high-risk

human to human.

populations.

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Beyond Lipids,
Towards Life...
Effects of 11 years Simvastatin on mortality
and morbidity follow up of the Heart
Protection Study (HPS)
First major vascular event during total follow-up period
50

Placebo
Simvastatin (Simtin)

Participants suffering events (%)

45
40

Prolonged Simvastatin
(Simtin) treatment produces
larger absolute reductions in
vascular events.(1)

35
30

Even after study treatment


stopped in HPS, benefits
persisted for at least 5 years
without any evidence of
emerging hazards.(1)

25
20
15
10
5
0
0

5
6
Follow-up (years)

10

11

(1) Heart Protection Study Collaborative Group; Effects on 11-year mortality and morbidity of lowering LDL cholesterol with Simvastatin for about 5 years in
20536 high-risk individuals: a randomized controlled trial; the Lancet, published online 23 November 2011. Doi: 10.1016/s0140-6736(11)61125-2.

Further information available upon request:


Hong Kong:
Tel: + 852 2562 6276

Singapore:
Tel: + 65 6553 4018

R E S E A R C H

F O R

T H E

Malaysia:
Tel: + 603 5512 9886

H U M A N

N E E D S

O F

T O M O R R O W

1 -31 Ja n ua ry 2 01 5

MA L AYS I A foc u s

19

CVD bigger killer than cancer, often


neglected
Pank Jit Sin

will lead to a big loss for the family and the country. Therefore, it makes sense to focus on CVD

ardiovascular diseases (CVD) have been

prevention and to create more awareness about

the main cause of death in the Malaysian

the disease. In fact, Robaayah said it was im-

population since 2007. This trend has contin-

portant to keep reminding the public as well as

ued, with the number of people dying from CVD-

healthcare personnel about CVD so that they

related causes increasing year on year.

wont forget about the disease. This is impor-

Tan Sri Robaayah Zambahari, senior consul-

tant both for those already suffering from CVD

tant cardiologist, National Heart Institute, said

who are undergoing treatment (statins, blood

the call to place more attention on heart and

thinners, etc), and for those who have not yet

circulatory diseases (collectively known as car-

developed the disease, to ensure that they do

diovascular diseases) is timely and appropriate,

not ignore their health.

as CVD kill more people a year than all cancers.


Robaayah said the urgency and importance of

Prevent and treat risk factors

dealing with CVD is all too commonly drowned

Robaayah said CVD could be prevented by pre-

out by concern with other diseases and happen-

venting its risk factors, namely obesity, diabetes,

ings.

hypertension and hypercholesterolemia. Aware-

The call to address CVD is particularly im-

ness and reminders will mean that people will

portant in Malaysia, as according to Malaysias

monitor their own condition; this will serve to al-

own National Cardiovascular Diseases (NCVD)

low detection of risk factors early and thus allow

Registry, our population develops CVD about 7

people to be treated early. Early treatment before

to 8 years earlier, at 59 years, than the global av-

heart damage and scarring occur will greatly re-

erage of 66 years, as determined by the Global

duce disability and also prevent death. Many of

Registry of Acute Coronary Events (GRACE).

the risk factors associated with CVD, such as

Whats more alarming in this country is that 49

hypertension and hypercholesterolemia, are si-

percent of those afflicted with CVD fall in the 40

lent. This makes CVD another silent killer.

to 60 year age group.

For those with one or two risk factors, lifestyle

Speaking to the media at a CVD awareness

modifications such as exercise and diet moni-

session, Robaayah said: As you can see, these

toring are sufficient to bring the person back to

are people in the prime of their lives. These

health. However, a person with severe dyslip-

people are still productive; if they are stricken

idemia may need medication to aid in balanc-

with a heart attack or associated disease, this

ing cholesterol levels. Typically, statins, fibrates,

1 -31 Ja n ua ry 2 01 5

ternational

inhibitors can be used to help lower cholesterol

said the trial provided sufficient evidence that

levels. Statins are usually the drug of choice to

dual therapy with a statin plus cholesterol ab-

address dyslipidemia. In cases where mono-

sorption inhibitor provided better reduction

therapy is insufficient, additional agents such as

of LDL cholesterol compared to statin alone

nicotinic acid or cholesterol absorption inhibi-

in patients with recent acute coronary syn-

tors may be added.

drome. The reduction in cholesterol levels also

Reduction of Outcomes: Vytorin Efficacy In-

(IMPROVE-IT),

20

resins, nicotinic acid and cholesterol absorption

Alluding to the recently published Improved

Trial

MA L AYS I A foc u s

Robaayah

correlated to a reduction of major vascular


events.

1 -31 Ja n ua ry 2 01 5

Co n fe r e n ce Cov e r ag e

22

Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia

When should physicians stop HBV


therapy?
Radha Chitale

new schema for when to stop hepatitis B


virus (HBV) therapy that stratifies patients

by viral genotype could provide a roadmap for


hepatologists in the Asia-Pacific region for improving patient outcomes, said Dr. Muhammad
Umar, of the Centre for Liver and Digestive Diseases at the Holy Family Hospital in Rawalpindi,
Pakistan.

add an alternative therapy and receive extreme-

Globally, about 2 billion people have or have

ly close monitoring if they have inadequate vi-

had an HBV infection. Up to 40 percent develop

ral response. However, seroconversion, which

liver failure or hepatocellular carcinoma (HCC)

is widely accepted as the primary endpoint for

and about 1 million people die each year from

HBV treatment, is not useful for certain types of

HBV-associated liver disease. [WHO Fact Sheets,

less responsive HBV patients those who are

www.who.int; N Engl J Med 1997;337:1733-45]

HBV e antigen (HbeAg)-negative mutants in the

HBV patients can be categorized into three


groups: complete viral response (viral load <60
IU/mL), partial or response (viral load >60 to

precore and core promoter regions.


For these patients relapse is common after
stopping oral therapy.

2,000 IU/mL), and inadequate response (viral

Therapy is usually administered long-term,

load 2,000 IU/mL). These are determined after

Umar said. But several years of undetectable

patients are assessed for primary non-response

HBV DNA may decrease the relapse rate.

after starting treatment at week 12 and again for

By comparison, in HBeAg-positive patients,

early predictors of efficacy via viral load at week

who are the wild type, seroconversion can be

24. [Keeffe EB et al. Clin Gastroenterol Hepatol.

used to measure whether the HBV viral load has

In press.]

reduced and, when it becomes low or unde-

Based on the viral response, patients may

tectable, therapy may be discontinued 6 to 12

have no change in treatment and broadened

months after seroconversion. However, Umar

monitoring, no change in treatment and close

said the durability of response would be about

monitoring, or they may need to switch to or

80 percent.

international
Digestive
Disease
Forum

2015

6 7 June 2015 | Hong Kong

call for abstract

young
investigator
award

Outstanding abstracts will be


published as electronic abstracts in
Clinical Gastroenterology & Hepatology
(Impact Factor: 6.5)

ORGANIZING COMMITTEE
Chairman: Justin C. Y. Wu
Members: Francis K. L. Chan
Henry L. Y. Chan
Philip W. Y. Chiu
Kelvin L. Y. Lam
Siew C. Ng
Raymond S. Y. Tang
Grace L. H. Wong
Vincent W. S. Wong
Jun Yu

SECRETARIAT
MIMS (Hong Kong) Limited
Tel: (852) 2155 8557
Fax: (852) 2559 6910
Email: info@iddforum.com

Pioneering Research and Practice


Please submit your abstract NOW! Deadline: 31 March 2015

www.iddforum.com

1 -31 Ja n ua ry 2 01 5

Co n fe r e n ce Cov e r ag e

24

Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia


Radha Chitale reports

Improving CRC risk stratification


through simple criteria scores

isk stratification in colorectal cancer (CRC)


patients with the Asia-Pacific CRC Screen-

ing (APCS) score can help reduce the risk of


morbidity and mortality from CRC, but barriers
remain against screening uptake.
We anticipate [APCS] will be easier to use
in clinics by GPs for assessing the risk of CRC,
be a more efficient use of the resources and

Lifestyle factors, particularly smoking and

manpower, and improve public awareness via

weight, are significant contributors to higher

self-assessment of CRC risk, said Clinical As-

CRC risk. Metabolic syndrome increases the

sociate Professor Han-Mo Chiu, of the National

risk of proximal and synchronous neoplasms,

Taiwan University and Hospital and the Asia-Pa-

Chiu said, as well as advanced neoplasm oc-

cific Working Group on Colorectal Cancer.

currence.

The APCS score is a simple set of criteria

Increasing physical activity, reducing waist

that classifies patients into average, moder-

circumference, smoking and alcohol intake, and

ate and high CRC risk based on age, gender,

improving diet can reduce the risk of CRC by 23

family history of CRC and smoking status. [Gut

percent. [BMJ 2010;341:c5504]

2011;60:1236-1241]

Coupling primary prevention via lifestyle

The Asia-Pacific region has a low rate of

changes with increased early screening has the

screening, ranging from about 33 to 40 percent

potential to reduce the risk of CRC in at-risk pa-

across Taiwan, Japan, Korea and, at the high

tients, particularly in the Asia -Pacific region. US

end, Australia. Low public awareness is part of

data from 1975 to 2006 has shown that screen-

the problem, but physicians play a key role in

ing and early treatment contributed to half of the

recommending screening.

CRC incidence reduction (26 percent) during

Current international guidelines recommend

that period. Reduced mortality was attributed

screenings about every 10 years if a colonos-

in significant part to risk factor modification (35

copy is normal or if there are small adenomas,

percent) and screening (53 percent) and only

and every 3 years if there are more than three

partially to advances in CRC treatment (12 per-

adenomas or one advanced neoplasm.

cent). [Cancer 2010;116:544-73]

1 -31 Ja n ua ry 2 01 5

Co n fe r e n ce Cov e r ag e

25

Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia


Radha Chitale reports

Early surgery may benefit Crohns


disease patients

he incidence of Crohns disease is increas-

aphoresis. Surgery, in addition to medication

ing in Asia and besides medical treatment

and nutritional therapy, is recommended for se-

and dietary changes, earlier surgery may be an

vere Crohns disease. [MHLW Research Group

appropriate treatment option, research shows.

Report 2013]

Crohns disease, a type of inflammatory

For people whose Crohns disease is local-

bowel disease that can affect the entire gastro-

ized in the distal ileum, surgery may be an ap-

intestinal tract, is on a steady upward trend in

propriate early intervention, Sugano said, with

countries including Hong Kong, Korea and Ja-

beneficial long-term recurrence rates.

pan, according to Dr. Kentaro Sugano, of Jichi

In one study of 55 patients with Crohns dis-

Medical University in Shimotsuke, Tochigi, Ja-

ease who underwent resection surgery, over a

pan.

median 6.7 years of follow up, 32 patients re-

In general, international guidelines suggest

mained relapse-free. Five patients required re-

beginning with anti-inflammatory medications

section for recurrent disease but body image

and incorporating digestible nutrients into an

and comesis scores improved overall. [Br J

elemental diet composed of easily digestible

Surg 2010;97:563-8]

liquid amino acids, fats, sugars, minerals and

Taking into account the benefits and risks of

vitamins, in patients with mild-to- moderate

medical treatment and surgery, the risk of recur-

Crohns disease.

rence after surgery, individual preferences and

This may be followed by more medications


(antibiotics,

immunosuppressants,

cortico-

steroids), nutritional therapy, and granulocyte

any personal or cultural considerations, surgery


can be less expensive and may have a better
long-term outcome, Sugano said.

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1 -31 Ja n ua ry 2 01 5

Co n fe r e n ce Cov e r ag e

27

Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia Elvira
Manzano reports

Challenges in the management of


acute severe ulcerative colitis

cute severe ulcerative colitis remains a


challenging condition to manage even in

the era of biologic therapy, says an expert.


Ulcerative colitis is a chronic, idiopathic inflammatory disorder with significant morbidity
and mortality, said Associate Professor Ida Hilmi, a consultant in gastroenterology, University
of Malaya, Kuala Lumpur, Malaysia. The clinical course of the disease typically manifests
with remissions and exacerbations character-

ized by rectal bleeding and diarrhea. Medical


therapy can only ameliorate the inflammatory

pseudomembranous colitis can complicate or

process and control most symptomatic flares

mimic severe ulcerative colitis. Plain abdomi-

but provides no definitive treatment for the dis-

nal radiographs are also important to look for

ease.

toxic megacolon or to rule out perforation.

Acute severe ulcerative colitis is usually de-

For patients who meet the clinical criteria for

fined according to the original criteria set forth

severe ulcerative colitis, sigmoidoscopy and a

by Truelove and Witts frequent loose bloody

biopsy may be required to look for cytomega-

stools (6 per day) with evidence of systemic

lovirus (CMV), the presence of which may re-

toxicity as demonstrated by fever (37.8C),

sult in treatment failure. Endoscopic scoring

tachycardia (heart rate [HR] >90 bpm), ane-

system (eg, the modified Baron score) may

mia (Hb <10.5 g/dL) or an elevated erythrocyte

be used to assess for disease severity. Some

sedimentation rate (HR) >30 mm/h.

patients, however, may have severe ulcerative

Clinicians should be able to rule out precipitating or other causes and assess the need

colitis at endoscopy, despite not fulfilling the


clinical criteria for severity, said Ida.

for emergent surgery, Ida said. Stool micros-

Intravenous corticosteroids (hydrocortisone

copy and culture should be performed as part

100 mg four times daily or methylprednisolone

of the initial assessment, as well as a test for

60 mg daily) remain the mainstay of treatment

Clostridium difficile infection. This is because

for severe ulcerative colitis. Careful monitoring

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

28

of stool frequency and vital symptoms, as well

severe ulcerative colitis refractory to intrave-

as abdominal examination, is necessary to as-

nous steroids. [Lancet 2012;380:1909-5]

sess the patients response to therapy. The use

Well-timed rescue medical therapy is

of antibiotics may be justified in those with co-

generally safe when administered by experi-

existing sepsis, she added.

enced physicians, and is effective in the ma-

For patients with steroid-refractory colitis,

jority of cases, said Ida. Close liaison with

rescue therapy with cyclosporine or infliximab

the surgeon is essential as the window for

must be commenced. In one study, intrave-

timely surgery is narrow and delayed surgery,

nous infliximab was no more effective than in-

when it is required, can lead to significant

travenous cyclosporine in patients with acute

complications.

READ JPOG ANYTIME, ANYWHERE.


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1 -31 Ja n ua ry 2 01 5

Co n fee n ce Cov e r ag e

29

Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia Elvira
Manzano reports

Serologic and fecal biomarkers in IBD:


Can they replace endoscopy?

here is a need for simple tests to assist


the accurate diagnosis and prognostic as-

sessment of patients with inflammatory bowel


disease (IBD), says an expert.
Serological antibodies are helpful in this
setting, but with major limitations, said Professor Michael A. Kamm, of St. Vincents Hospital and the University of Melbourne, Australia.
Most of the described antibodies found in IBD
are autoantibodies directed against enteric
microbial epitopes and are thought to arise
secondary to the disease process but are not
thought to play a pathogenic role.

2013;19:6207-13]

Perinuclear antineutrophil cytoplasmic an-

Of note, none of the currently available sero-

tibodies (pANCA) and anti-Saccharomyces

logical markers for IBD can be used as a stand-

cerevisiae antibodies [ASCA], for example,

alone diagnostic in clinical practice and can

may have diagnostic value and are helpful in

only serve as an adjunct to endoscopy, which

distinguishing Crohns disease (CD) from ul-

is quite invasive.

cerative colitis (UC) and intestinal tuberculosis

As clinical aid, C-reactive protein (CRP) has

(TB). However, they have limited prognostic

been the typical laboratory marker used for

value, said Kamm. There is the presence of

differentiating IBD from functional and other

a large number of detectable antibodies [in the

bowel disorders. CRP is an objective marker of

serum] that are associated with worse long-

inflammation and correlates well with disease

term prognosis.

activity in CD. However, it is still far from ideal,

Clinicians should also keep in mind that

said Kamm.

antibody incidence in IBD is affected by spe-

It is nonspecific measures inflammation

cific disease, geography and ethnicity. Hence,

but it does not tell us where the inflamma-

serologic responses differ between Asian and

tion is occurring. There is also remarkable

Western populations. [World J Gastroenterol

heterogeneity in the CRP response between

1 -31 Ja n ua ry 2 01 5

CD and UC.

CO N F E R E N C E COV E RAG E

30

useful in distinguishing IBD from functional

Recently, several fecal biomarkers have

symptoms and in monitoring disease recur-

been developed that are sensitive indicators of

rence. Fecal testing of calprotectin can also in

active intestinal inflammation and may provide

some circumstances replace endoscopy.

a convenient method to assist in the diagnosis

Fecal calprotectin is easy to measure, and is

and prognosis of patients with IBD. The best

reproducible. The test is also inexpensive. Fe-

proven biomarker is calprotectin, a neutrophil-

cal calprotectin is likely to play an increasingly

derived protein which is stable in feces and

important role in the management of IBD, Kamm

can be quantitatively measured in stool. It is

said.

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

31

Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia

Novel therapeutic interventions for


gastroparesis
Elvira Manzano

he treatment of gastroparesis delayed


gastric emptying in the absence of mechan-

ical obstruction is targeted at symptom control


and correcting the precipitating cause of gastric
stasis, says an expert.
In patients with diabetes, gastroparesis and
the associated disturbance in the delivery of nutrients into the duodenum may affect the ability to properly control glucose, said Professor
Gerald Holtmann, of the department of gastroenterology and hepatology, Princess Alexandra Hospital and the University of Queensland

Inhibiting acetylcholinesterase activity to im-

in Brisbane, Australia. Gastroparesis is also

prove gastric motility and emptying is also an-

thought to play an important role in the mani-

other therapeutic approach, said Holtmann.

festation of symptoms in patients with functional

Erythromycin derivatives devoid of antibiotic

dyspepsia. Thus, normalization of gastric emp-

properties are also considered promising candi-

tying may be targeted to relieve symptoms in

dates for the treatment of gastroparesis. Eryth-

patients with functional dyspepsia or to control

romycin given at low doses stimulates gastro-

glucose in those with diabetic gastroparesis.

intestinal motility and substantially accelerates

Apart from diabetes, common causes are

gastric emptying, he added.

idiopathic and post-surgical as a consequence

Interestingly, normalization or improvement

of vagal nerve injury following upper abdominal

of gastric emptying in response to prokinetics is

surgery, resulting in reduced pyloric relaxation

not linked to improvement in symptoms. In one

and impaired antral contraction.

study, for example, treatment with ABT-229, an

Pharmacologic management include medi-

erythromycin derivative, was no more effective

cations targeting dopaminergic or serotoniner-

than placebo in relieving symptoms in patients

gic pathways such as metoclopramide, dom-

with or without delayed gastric emptying. Upper

peridone, cisapride, prucalopride, or itopride.

abdominal discomfort severity scores were simi-

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

32

lar between the two groups at 4 weeks. [Aliment

terventions [pyloro-myotomies, gastro-jejunos-

Pharmacol Ther 2000;14:1653-61]

tomies] have been used to treat gastroparesis,

For patients with refractory gastroparesis,

transpyloric stents have been trialled in selected

gastric electrical stimulation has been shown to

cases. Symptom control appears successful,

reduce symptoms, particularly nausea and vom-

but there is questionable effect with regard to

iting, in small open-label studies. More recently,

other outcome parameters, said Holtmann.

intrapyloric injection of botulinum toxin has been

For refractory patients who have failed other

successfully trialled in a small group of patients.

measures, a gastrectomy may be the only op-

While traditionally more invasive surgical in-

tion.

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1 -31 Ja n ua ry 2 01 5

Reg io n a l

34

IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting 2014, November 1416, Taipei, Taiwan Chuah Su Ping reports

Soy isoflavones and carotenoids


have gender-specific protective roles
against hip fractures

oy food intake is associated with a


reduced risk of osteoporotic hip fractures in women but not in men, accord-

ing to research from the Duke-NUS Graduate


Medical School, Singapore. More recent data
from the same study, the Singapore Chinese
Health Study, also suggest that adequate intake of carotenoids may reduce the risk of osteoporotic fractures among elderly men, but
not in women.

Total soy isoflavone intake for a given sub-

The incidence of hip fractures is rising in

ject was computed based on the food frequen-

Asia, in part due to the rapidly aging popula-

cy questionnaire (which all participants were

tion, however there is still a paucity of studies

required to complete) and the summation of

among Asian populations on the dietary factors

the [isoflavone] content of all the seven soy

of osteoporosis, said Duke-NUS researcher

foods in the Singapore Food Composition Da-

Associate Professor Koh Woon Puay. Koh and

tabase, she said.

her team prospectively examined the associa-

This is the first study to compare the effects

tions of dietary intakes of soy isoflavones and

of soy on hip fracture between men and wom-

carotenoids with hip fracture risk among el-

en in a cohort study, noted Koh. Our study

derly Chinese in the Singapore Chinese Health

revealed a significant reduction in hip fracture

Study, a prospective cohort of 63,257 men and

in women with moderate intakes of soy isofla-

women 45 to 74 years of age.

vones. Conversely, no protective association

In their paper, Koh and colleagues noted


that soy food products, such as plain tofu,

was found in men with similar intakes. [Am J


Epidemiol 2009;170:901-9]

taupok, taukwa, foopei, foojook, tofu-far and

Koh noted that this is consistent with previ-

soybean-drink, are common in the Singapore

ous animal studies which showed that expo-

Chinese diet.

sure to the isoflavone genistein was linked to

1 5-31 D ecembe r 2 01 4

R E G I O NAL

35

increased bone marrow density in the femurs

(BMI <20 kg/m2), said Koh. There was no

of adult female mice but not in male mice. [Pe-

association between dietary carotenoids or

diatr Res 2007;61:48-53]

vegetables/fruits, and hip fracture risk among

With regards to carotenoid intake and hip

women. The authors postulated that the anti-

fracture risk, Koh noted that among men, con-

oxidant effects of carotenoids may counteract

sumption of vegetables the main source of

the mechanism of osteoporosis related to lean-

carotenoid intake in this population was as-

ness. [J Bone Miner Res 2014;29:408-17]

sociated with lower hip fracture risk. Similarly,

Koh concluded that, based on the hypoth-

dietary intake of total carotenoids and specific

eses attained from these two studies, future

carotenoids -carotene, -carotene, and

interventional studies should target different

lutein/zeaxanthin were inversely associated

mechanisms in osteoporotic fractures.

with hip fracture risk.

high

resolution

micro-computed

tomo-

When stratified by body mass index (BMI),

graphic imaging, our goal is to further assess

the greatest protective effects of total vegeta-

the relationship between bone microstructure

bles and carotenoids were found in lean men

and fracture risk.

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1 -31 Ja n ua ry 2 01 5

Reg io n a l

37

IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting 2014, November 1416, Taipei, Taiwan Chuah Su Ping reports

Odanacatib promising therapy for


osteoporosis in men

danacatib, a selective inhibitor of cathepsin K, has demonstrated promising po-

tential for the treatment of osteoporosis in men,


according to new results from the Long-Term
Odanacatib Fracture Trial (LOFT), which were
presented at the 5th Asia-Pacific Osteoporosis
Meeting held in Taipei, Taiwan. [Osteoporos Int
20 14;25:571(OC1)]
In a phase II study in postmenopausal

assess the effect of odanacatib 50 mg weekly

women, treatment with odanacatib 50 mg once

versus placebo on lumbar spine BMD over 24

weekly resulted in increases in bone mineral

months; and to assess the safety and tolerabil-

density (BMD) at the lumbar spine (11.9 per-

ity of odanacatib 50 mg weekly compared with

cent) and total hip (8.5 percent) over 5 years,

placebo. We enrolled men 40 to 95 years of

said Professor Eric Orwoll, director of the Bone

age with idiopathic osteoporosis or osteoporo-

and Mineral Clinic, and of the Bone Density Lab

sis associated with hypogonadism (total serum

at Oregon Health and Science University, Port-

testosterone 250 ng/dL). Participants were

land, US. [J Bone Miner Res 2012;27:2251-5]

randomized to either the study drug or placebo

Men with osteoporosis represent between

once weekly, and all received vitamin D3 (5,600

20 and 25 percent of all osteoporotic patients

IU/week) and calcium supplements (total intake

and men are at greater risk of death following a

approximately 1,200 mg daily), noted Orwoll.

hip fracture. Following the promising results of

Compared with placebo, treatment with

the phase II study in postmenopausal women,

odanacatib 50 mg weekly for 24 months in-

we carried out a double-blind, placebo-con-

creased lumbar spine, total hip, femoral neck

trolled 24-month study to evaluate the safety

and trochanteric BMD. We noted decreased

and efficacy of odanacatib for the treatment of

levels of markers of bone resorption in the

men with osteoporosis, said Orwoll. This is

odanacatib group versus placebo. While mark-

the first study of odanacatib in men with osteo-

ers of bone formation initially decreased [in the

porosis.

odanacatib group], these were then noted to

The primary objectives of their study were to

return toward levels similar to that observed in

1 -31 Ja n ua ry 2 01 5

F e atu r e

38

the placebo group by month 24, said Orwoll.

bone turnover markers suggest that odana-

The investigators noted that the adverse events

catib treatment decreases bone resorption

and overall safety profile were similar between

while producing relatively small decreases in

both study groups.

bone formation. Thus, this cathepsin K inhibi-

These data indicate that odanacatib ther-

tor may be a promising potential therapy for

apy is effective in increasing spine and hip

the treatment of osteoporosis in men, Orwoll

BMD in men with osteoporosis. Changes in

concluded.

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Sponsored Symposium Highlights

Intensification of Insulin:

Premixed vs Basal Prandial

On the 8th of November 2014, a symposium in Malacca saw a distinguished speaker from Australia speak on
the intensification of insulin in the management of type 2 diabetes (T2D), and the comparison between basal
vs premixed insulin. Below are highlights from his presentation.

The glucose triad


The optimal management of T2D requires an understanding of
the relationships between glycosylated haemoglobin (HbA1c),
fasting plasma glucose (FPG) and postprandial glucose (PPG).
This relationship is called the glucose triad and the management
of T2D needs to take into account how these three factors change
during the development and progression of the disease.1
For instance, significantly high PPG excursions can occur in
individual whose HbA1c is within target. Hence, intervention
should not focus only on HbA1c but also acute glucose swings
or glycaemic variability, as the later has been shown to exhibit a
more specific triggering effect on oxidative stress than chronic
sustained hyperglycaemia. Oxidative stress plays a major role in
the development of vascular complications.2
The Diabetes Epidemiology: Collaborative analysis Of Diagnostic
criteria in Europe (DECODE) study also found that while FPG alone
does not identify individuals at increased risk of death associated
with hyperglycaemia, mortality risk was found to increase with
increasing 2-hour PPG, independent of FPG.3
According to the International Diabetes Federation (IDF)
guidelines, the growing body of evidence now suggests that
reducing PPG excursions is as important, or perhaps more
important than FPG for achieving HbA1c goals. The guidelines
agreed it is important to manage both postmeal and fasting
glycaemia to optimise control and treatment should be initiated
simultaneously at any HbA1c level. The guidelines also agreed that
postmeal hyperglycaemia is associated with cardiovascular (and
other) risks, and the treatment target of 2-hour PPG <7.8mmol
(<140 mg/dl) is reasonable and achievable.4
Studies such as the United Kingdom Prospective Diabetes
Study (UKPDS) have shown that early and sustained control of
glycaemia is important in the management of T2D.5 However
there is a risk of treatment inertia among clinicians. Data
showed that the average patient accumulated nearly five years
of excess glycaemic burden >8.0% from diagnosis until starting
insulin and about 10 years of burden >7.0%. In short, patients
who are not achieving glycaemic targets should have their
treatment changed earlier to prevent unnecessary exposure to
hyperglycaemia for prolonged periods and thus reduce the risk
of developing complications.6

Insulin intensification
Failure to advance therapy could occur when the need arises to
add insulin to oral therapy or during insulin intensification.
Clinicians should consider intensifying treatment with mealtime
insulin regimens when combination therapy (oral antidiabetic
agent + basal insulin) fails to achieve HbA1c targets (7%) after 3-6
months; and when significant PPG excursions occur (e.g. to >10.0
mmol/L [>180 mg/dL]). This is suggested when FPG is at target
but the HbA1c remains above goal 3-6 months after basal insulin
titration.7
According to Associate Professor Chen, while guidelines offer
various recommendations for insulin intensification, it is good
practice to intensify insulin according to the individuals needs.
However, notable proportions of primary care physicians never
initiate or modify insulin and never or rarely intensify insulin.
The main barriers to insulin intensification cited were lack of
experience and lack of time to educate patients.8
Intensification of insulin also brings along its own challenges.
While the transition from one to two injections daily has not
been shown to result in patient-reported increase in burden,
the transition to three or four daily injections can significantly
increase patient burden.9 Due to the perceived burden of the
multiple daily injections, patients may intentionally skip their

insulin dose.10 Thus, intensification to basal bolus may not be


suitable for some patients.

(p=0.56). There were more premixed patients achieving


HbA1c<7% compared with glargine (52.6% vs 43.2%, p=0.005).
In addition, there was no difference in severe symptomatic
hypoglycaemia between the two groups.14

One strategy in intensifying insulin therapy is a stepwise


approach, where mealtime insulin is added at the biggest meal
of the day and titrated to two or more mealtime insulin. Although
this strategy is more practical than moving to full basal-bolus
therapy requiring multiple daily injections, it can be very complex
to execute.11

In another study called the LanScape study, T2D patients who


were already on basal insulin were assessed. This international,
controlled trial randomized patients to receive insulin glargine
and glulisine OD or biphasic insulin aspart 30 BD.15

A second, more convenient but less adaptable method involves


twice daily premixed insulin, consisting of a fixed combination of
an intermediate insulin with regular insulin or a rapid analogue.
This strategy may be appropriate for patients who eat regularly
and may be in need of a simplified approach. Premixed insulin
offers effective HbA1c lowering after basal insulin, requires fewer
injections than basal-bolus and reduces the complexity that is
associated with full basal-bolus.7,12

At 24 weeks, HbA1C decreased by 1.00% in the glargine+glulisine


group and 1.22% in the biphasic group, implying non-inferiority
between the two groups (Figure 2). There was no significant
difference in weight change between the two treatment groups
as well. While there was no difference in overall hypoglycaemia
rates (15 vs 18 events/patient-year respectively p=0.2), there was
slightly more nocturnal events with glargine+glulisine (5.7 vs. 3.6
events/patient-year p=0.02) (Figure 3).15

Clinicians may choose to switch to modern premixed insulin from


basal bolus due to the various benefits, including the following:
Less complex
Easy to titrate
Patient compliance
Effective HbA1c reduction
Less hypoglycaemia.

Figure 2: Biphasic insulin aspart 30 offers


comparable efficacy in reducing HbA1c as basal
prandial

According to a practical guideline by Unnikrishnan et al, patients


may be switched to biphasic insulin aspart 30 once the daily
basal dose reaches 0.5 Ukg. Figure 1 is a simple algorithm for the
intensification of basal insulin therapy to biphasic insulin aspart
30/70.13

Figure 1: A simple algorithm for the intensification


of basal insulin therapy once daily (OD) or twice
daily (BID) (analogue or human) to biphasic
insulin aspart 30/70 (BIAsp 30) BID. FPG, fasting
plasma glucose
Basal insulin OD or BID

HbA1c 7-8%
FPG > 6 mmol/l
(FPG > 110 mg/dl)

LanScape: HbA1c
Primary endpoint: HbA1c

Basal plus
-0.2
-0.4
-0.6
-0.8
-1

Switch to BIAsp 30 BID

Evidence from clinical trials


Patients may benefit from premixed insulin when used as
initiation or intensification of insulin regimen, as the clinical trials
have demonstrated.
One of these trials is the GALAPAGOS study, which was a 24week, open-label, multinational, superiority trial of glargine (
glulisine) compared with premixed insulin in insulin-nave T2D
patients uncontrolled on oral antidiabetic drugs. Patients were
randomised to glargine OD or premixed insulin (OD or BID) while
continuing the oral drugs. A second premixed injection could be
added any time; while glulisine could be added with main meal
in glargine patients with HbA1C 7% and FPG <126 mg/dL at
week 12. Insulin titration targeted FPG 100 mg/dL.14
Results showed that the mean change for HbA1c was -1.5% in the
glargine group vs -1.6% in the premixed group (p=0.008). The
mean change for FPG was greater in the glargine group (-53.3
vs -47.2 mg/dL) (p<0.001), while the mean change for PPG was
-44.0 in the glargine group and -50.0 in the premixed group
(p=0.024).14
At the end of the trial, 33.2% of those on glargine and 31.4%
of those on premixed achieved the primary endpoint of
HbA1c<7% at study end with no symptomatic hypoglycaemia,
hence demonstrating non-inferiority between the two regimen

-1.22

-1.4

Mean (SE) difference


0.21 (0.09), NS

Vora et al. Diabetes 2013;62(Suppl. 1B):47-LB

Figure 3: Biphasic insulin aspart 30 offers


significantly lower incidence of nocturnal
hypoglycaemia compared with basal prandial

HbA1c 8.0%

Int J Clin Pract, November 2009, 63, 11, 1571=1577

-1

-1.2

BIAsp, biphasic insulin aspart; NS, not significant

Hypoglycaemia

NS difference

FPG: 4-6 mmol/l


(FPG > 73-110 mg/dl)

Titrate basal insulin to


achieve
FPG < 6 mmol/l
(FPG < 110 mg/dl)

BIAsp 30

Change from baseline in


HbA1c(%)

Director of Diabetes Services


Deputy Head of Endocrinology
Department of Endocrinology and Metabolism,
Concord Repatriation General Hospital
Sydney, Australia

20
Incidence: episodes/year

Associate Professor Roger Chen

18
16

18.2
15.3
Significantly lower
with BIAsp: p=0.019

14
12
10
8

5.7

*
3.6

4
2
0
Overall
hypoglycaemia

Basal plus

Nocturnal
hypoglycaemia

Biphasic

According to Associate Professor Chen, another way to intensify


basal insulin therapy is to consider premixed insulin. Premixed
insulin may be considered when the basal dose exceeds 40 units,
but the PPG is still not controlled and patient experiences fasting
hypoglycaemia. This can be accomplished by changing the dose
of the basal insulin for another dose of premixed insulin, and
injecting at a meal when the patient experiences the highest
PPG surge.
A look at real world data also showed the importance of
intensifying insulin to achieve target glucose levels, and
how intensification to premixed insulin may further improve
glycaemic control.

Evidence from real world data


The A1chieve study is a 60,000-person, global, prospective,
observational study, which sought to evaluate the adverse
events and effectiveness of premixed (biphasic insulin aspart

The A1chieve study also found that


24 weeks after switching from basalbolus insulin regimens to biphasic
insulin aspart 30, glycaemic control
and health-related quality of life
were significantly improved, and
hypoglycaemia was significantly
reduced (Figure 4). Hence those who
are inadequately controlled on basalbolus insulin regimens can consider
biphasic insulin aspart 30.18
In this respect, biphasic insulin aspart
30 regimens can be optimised through
simple self-titration algorithms, which
enable easy intensification of insulin
therapy and may lead to improved
quality of life for the patient through
better adherence and improved
glycaemic control.
Another
large,
multi-national,
multicentre, prospective, observational
study, PRESENT found that initiating
or transferring uncontrolled patients
from human insulin to biphasic insulin
aspart improved glycaemic control.19
This study confirmed that titration is
important to get patients to target.
In summary, due to the progressive
nature of T2D, insulin will be
necessary in most patients. Insulin
regimens used will have to depend
on the patients lifestyle patterns
and needs, as well as the clinicians
regular practice. Studies have
shown that once-daily premixed
insulin and once-daily basal insulin
regimens are largely similar in terms
of glycaemic control and tolerability.
Glycaemic control with twice-daily
premixed insulin is shown to be
better than with basal regimens,
with similar tolerability. In addition,
intensification from twice daily to
thrice daily premixed can result in
further improvements in glycaemic
control.20 The intensification of
premixed insulin is simplified by the
use of the same injection device and
insulin, hence preventing potential
mix ups.13

Key Messages:
1.

2.

3.

4.

5.

Biphasic insulin aspart 30 offers


efficacy comparable to basal
prandial.
Biphasic insulin aspart 30 offers
significant lower incidence of
nocturnal hypoglycaemia.
Biphasic insulin aspart 30 offers
a simplified regimen: one insulin
in one device is all the patient
needs for both PPG and FPG
coverage.
With
similar
number
of
injections, biphasic insulin
aspart 30 twice daily offers two
PPG and basal coverage, while
basal plus one prandial (two
injections) only provide one PPG
and basal coverage.
American Diabetes Association
(ADA) and the European
Association for the Study of
Diabetes (EASD) 2012 stated
that basal plus two or more

Figure 4: Mean plasma HbA1c improved when patients switched to biphasic insulin aspart
30 from glargine- or neutral protamine Hagedorn-based basal-bolus insulin regimens.

10.5

Baseline (after starting biphasic insulin aspart 30)

Week 24

9.5
9
8.5
8

***

7.5
7

injections is a complex regimen.


Twice daily premixed insulin
may provide a more simplified
approach.
References:

10
HbA1c(%)

30), basal (insulin detemir), and mealtime (insulin aspart) insulin analogs
in people with T2D in near-routine
clinical practice.16 A lesson to be learnt
from this study is that improvements
in glycaemic control can be achieved
with an increase in the daily insulin
dose, and intensification of insulin
therapy.16,17

Glargine-based basal-bolus
insulin regimen

This continuous medical education is supported by

***

NPH-based basal-bolus
insulin regimen

1. Ceriello A. Int J Clin Pract 2010;64(12):1705


1711. 2. Monnier L, et al. JAMA 2006;295:16811687. 3. The
DECODE study group* on behalf of the European Diabetes
Epidemiology Group. Lancet 1999;354:617621.
4. IDF.
2011 Guideline for Management of Post Meal Glucose in
Diabetes. 5. Holman RR, et al. N Engl J Med 2008;359:1577
1589. 6. Brown JB, et al. Diabetes Care 2004;27:15351540.
7. Inzucchi SE, et al. Diabetes Care 2012;35:13641379.
8. Cuddihy RM, et al. Diabetes Educ 2011;37(1):111123. 9. Vijan
S, et al. J Gen Intern Med 2005;20:479482. 10. Peyrot M, et al.
Diabetes Care 2010;33:240245. 11. Meneghini L, et al. Endocr
Pract 2011;17(5):727736. 12. Liebl A, et al. Diabetes Obes Metab
2009;11(1):4552. 13. Unnikrishnan AG, et al. Int J Clin Pract
2009;63(11):15711577. 14. Aschner P, et al. Diabetes 2013;62(Suppl
1):948-P. 15. Vora J, et al. Diabetes 2013;62(Suppl 1B):47-LB.
16. Shah SN, et al. Diabetes Res Clin Pract 2010;88(Suppl 1):S11S16.
17. El Naggar NK, et al. Diabetes Res Clin Pract 2012;3(98):408
413. 18. Dieuzeide G, et al. Prim Care Diab 2013; http://dx.doi.
org/10.1016/j.pcd.2013.07.005. 19. Sharma SK, et al. Curr Med Res
Opin 2008;24(3):645652. 20. Garber AJ, et al. Diabetes Obes Metab
2006;8:5866.
EYKS_NM30-MT_INT-WRITEUP-47_1.0_NOV2014_MYBN

Editorial development by MIMS Medical Education. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss
or damage howsoever arising is hereby disclaimed. 2014 MIMS. All rights reserved. No part of this publication may be reproduced by any process in any language without the written
permission of the publisher. Enquiries: MIMS Medica Sdn Bhd (891450-U), Level 3A, Luther Centre, No. 6, Jalan Utara, 46200 Petaling Jaya, Selangor, Malaysia.
Tel: (603) 7954 2910 Fax: (603) 7958 7853 E-mail: enquiry.my@mims.com Web site: www.mims.com
MY-NOV-204

Sponsored Symposium Highlights

After Metformin: Making Sense of the Complexity


At a recent symposium held in Malacca, Associate Professor Roger Chen was invited to talk on the role of glucagon-like peptide-1 receptor agonist (GLP-1 RA),
namely liraglutide, in the management of diabetes after metformin. Below are highlights from his talk.

Whats after metformin?

Achieving HbA1c goals remain suboptimal among adults with


diabetes.1 In Malaysia, statistics showed that only 22% of patients
achieved a target HbA1c of <7% in 2008.2 It has been shown that
good blood glucose control by virtue of early detection and better
treatment results in better quality of life due to reduced risk of
complications. This in turn leads to reduced total healthcare cost.3
Metformin is the most widely used first-line therapy for the
management of diabetes. Following that, various classes
of antidiabetic agents may be added on, and these include
dipeptidylpeptidase 4 (DPP-4) inhibitors and GLP-1 RAs.4 The
American Association of Clinical Endocrinologists state that the
choice of therapies should be individualised; including GLP-1 RAs,
followed by DPP-4 inhibitors as possible first-line monotherapies,
highlighting that these agents should be used earlier rather than
later in the management of diabetes.5
The choice of therapies should take into account the differences
among the various classes in achieving HbA1c reductions, the risk
of hypoglycaemia, effect on weight, and other side effects.4,6 For
example, liraglutide, a GLP-1 RA, has been shown to produce the
greatest reductions in HbA1c values across all baseline categories,
when compared with sitagliptin, glimepiride, rosiglitazone,
exenatide, and insulin glargine.7 Moreover, when assessed by the
composite outcome of HbA1c<7%, no hypoglycaemia, and no weight
gain, liraglutide is shown to be superior to the other commonly used
therapies.8

Role of incretin mimetics

SWCW_VICTOZA_MT-01_1.0_Jan2015_MY

Incretin mimetics, such as GLP-1 RA mimic the actions of native GLP1 hormone, which is responsible for a range of important biological
actions in the body. GLP-1 is responsible for glucose-dependent
insulin secretion, and inhibition of glucagon secretion. GLP-1 RA
also slows gastric emptying and exerts other effects on the pancreas,
brain, heart, liver, adipose tissue, and muscle.9

Effect and Action in Diabetes (LEAD)-2 study, glycaemic control was


found to be similar among the groups. Liraglutide also was associated
with a higher reduction in body weight and hypoglycaemia compared
with glimepiride.11 The glycaemic control associated with liraglutide
was sustained over two years, comparable to glimepiride. Liraglutide
was also well tolerated, and was associated with weight loss and a
low rate of hypoglycaemia when used in the long term.12

Liraglutide vs. DPP-4 inhibitor

In a head-to-head trial, liraglutide was found to be superior to


sitagliptin for the reduction of HbA1c and was well tolerated
with minimum risk of hypoglycaemia, when used as add-on to
metformin.13 Moreover, patient satisfaction was significantly better
with 1.8 mg liraglutide than sitagliptin.14
When patients on sitagliptin were switched to liraglutide after 52
weeks of treatment, HbA1c improved further (p<0.01 for 1.2 mg
liraglutide; p<0.0001 for liraglutide 1.8 mg) (Figure 1). In addition,
there was a significant reduction of body weight (p<0.0001 for both
1.2 mg and 1.8 mg).15 The additional glycaemic and weight reductions
observed after switching to liraglutide may be especially beneficial
for those patients not achieving glycaemic goals with sitagliptin, as a
bigger proportion of patients were able to achieve their HbA1c target
of <7.0% after the switch.15

HbA1c (%):

7.2

7.6

-0.2

-0.5

-0.2
-0.4

Sitagliptin to
liraglutide 1.2 mg
Sitagliptin to
liraglutide 1.8 mg

p<0.01

-0.6
-0.8

Liraglutide vs exenatide: change in HbA1c18,19


Baseline
HbA1c:

LEAD-6

DURATION-6

8.1%
8.2%
LEAD-6

8.4%
8.5%
DURATION-6

0.0
-0.2
-0.4
-0.6

-0.8

-0.8

-1.1

-1.0
-1.2
-1.4

-1.3

p<0.0001

-1.6

-1.5

p=0.002

Exenatide 10 g BID

Exenatide 2 mg OW

In summary

Clinical data suggest that liraglutide is effective early in the


treatment of type 2 diabetes, providing:
o
Improved glycaemic control.
o
Weight loss.
o
Low risk of hypoglycaemia.
o
High patient acceptance.

p<0.0001

Mean (1.96 SE); estimates are from a paired t-test of change in HbA1c from Weeks
52 to 78 from the Ext. 2 FAS, LOCF

GLP-1 RAs are able to elicit an insulin response by increasing GLP-1 to


a pharmacological level.10 GLP-1 RA such as liraglutide may also offer
more than mere HbA1c lowering in the treatment of diabetes. The
benefits on HbA1c, weight, and hypoglycaemia can be seen in various
comparative studies highlighted below.

Another study by Charbonnel et al compared the injectable strategy


(liraglutide) with the oral agent sitagliptin and found a 2.3 kg
reduction of body weight with the injectable strategy; while in terms
of hypoglycaemia, the injectable strategy reported fewer episodes
compared to oral.16

Liraglutide vs. sulfonylurea

Liraglutide vs. another GLP-1 RA

When once-daily liraglutide (0.6, 1.2, or 1.8 mg) was compared to


glimepiride 4 mg as add-on therapy after metformin in the Liraglutide

Figure 2

BID, twice daily; GLP-1RA, glucagon-like peptide-1 receptor agonist; HbA1C, glycosylated haemoglobin; OD,
once daily;OW, once weekly.

Change in HbA1c from weeks 52 to 78: sitagliptin-toliraglutide switch

0.0

When compared with another GLP-1 RA exenatide 10 g twice


daily, liraglutide 1.8 mg once daily provided significantly greater
improvements in glycaemic control (p<0.0001) (Figure 2; LEAD6).18 When compared with exenatide 2 mg once weekly, liraglutide
was again shown to provide greater glycaemic reductions (Figure
2; DURATION-6). The reduction in body weight was also better with
liraglutide than with exenatide 2 mg.19

Liraglutide 1.8 mg OD

Figure 1

Week 52

to human GLP-1 (thus providing a better response rate), while


exenatide has 53% amino acid homology.17

Change in HbA 1c (%)

University of Sydney
Director of Diabetes Services, Senior Staff Endocrinologist
Concord Repatriation General Hospital

Change in HbA 1c (%)

Associate Professor Roger Chen

While there are several GLP-1 RAs in the market, they differ in their
molecular structures. Liraglutide has up to 97% amino acid homology

Data also showed that GLP-1 RAs are more potent than DPP-4
inhibitors, producing higher HbA1c reduction, with this effect
sustained from 12 weeks to 52 weeks.
Switching from a DPP-4 inhibitor to GLP-1 RA may result in further
improvement in HbA1c and decrease in body weight.
Liraglutide may provide greater reduction in HbA1c compared
with exenatide, with an added benefit of further weight loss.

References:

1. Casagrande SS, et al. Diabetes Care 2013;36(8):22712279. 2. Mafauzy M, et al. Med J


Malaysia 2011;66(3):175181. 3. CORE/IMS based on newly diagnosed UKPDS cohort at age 52. 4. Inzucchi SE, et al.
Diabetes Care 2012;35:13641379. 5. Garber AJ, et al. EndocrPract 2013;19(2):327336. 6. Esposito K, et al. Diabetes
Obes Metab 2012;14(3):228233. 7. Henry RR, et al. EndocrPract 2011;17(6):906913. 8. Zinman B, et al. Diabetes Obes
Metab 2012;14(1):7782. 9. Baggio LL, Drucker DJ. Gastroenterology 2007;132:21312157. 10. Brown DX, Evans M.
J Nutr Metab 2012, Article ID 381713. 11. Nauck M, et al. Diabetes Care 2009;32:8490. 12. Nauck M, et al. Diabetes
ObesMetab 2013;15(3):204212. 13. Pratley RE, et al. Lancet 2010;375(9724):14471456. 14. Pratley RE, et al. Int J Clin
Pract 2011;65(4):397407. 15. Pratley RE, et al. Diabetes Care 2012;35:19861993. 16. Charbonnel B, et al. Diabetologia
2013;56:15031511. 17. Umpierrez GE, Meneghini L. EndocrPract 2013;19(4):718728. 18. Buse JB, et al. Lancet
2009;374(9683):3947. 19. Buse JB, et al. Lancet 2013;381(9861):117124.

This continuous medical education is supported by


Editorial development by MIMS Medical Education. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor.
Any liability or obligation for loss or damage howsoever arising is hereby disclaimed. 2014 MIMS. All rights reserved. No part of this publication may be
reproduced by any process in any language without the written permission of the publisher.
Enquiries: MIMS Medica Sdn Bhd (891450-U), Level 3A, Luther Centre, No. 6, Jalan Utara, 46200 Petaling Jaya, Selangor, Malaysia.
Tel: (603) 7954 2910 Fax: (603) 7958 7853 E-mail: enquiry.my@mims.com Web site: www.mims.com
MY-NOV-205

State-of-the-art treatment of allergic rhinitis


and urticaria with bilastine, a new non-sedating
second generation antihistamine
At a sponsored dinner symposium held concurrently with the 2014 Asian Pacific Society of Respirology in Bali,
Indonesia, Professor Ralph Msges, a global leader in otorhinolaryngology and allergology from the University of
Cologne, Germany, shared his perspective on the treatment of allergies and how bilastine is an improved option for
patients who need a potent and efficacious antihistamine that controls patients allergic symptoms without causing
drowsiness and that is suitable for use by many patient types.
Placebo (n=225)

Professor Ralph Msges

The Allergic Rhinitis and its Impact on Asthma (ARIA)


Guidelines and the European Academy of Allergy and
Clinical Immunology (EAACI) recommend the use of secondgeneration H1-antihistamines to treat AR and urticaria,
because of their favorable safety profile.2,6 Previously,
treatment options included cetirizine, desloratadine and
fexofenadine. An exciting upcoming addition to the current
treatment armamentarium is bilastine, a new non-sedating
second-generation H1-antihistamine with potent anti-allergic
activity that has been shown to be well-tolerated.

The Bilastine Advantage

The clinical use of bilastine is supported by preclinical studies


demonstrating its high selectivity for H1-receptors and its
lack of affinity for other histamine receptors or other receptor
subtypes. In vitro studies have proven that bilastine has higher
H1-receptor affinity and is more potent as an H1-antagonist than
cetirizine and fexofenadine.7 In vivo studies have corroborated
the results obtained from in vitro experiments and shown that
bilastine has antihistamine and anti-allergic activity similar to
that of cetirizine and greater than that of fexofenadine.8
Data from pharmacokinetic and pharmacodynamic analyses
have proven that bilastine provides fast and effective relief of
allergic symptoms. Rapidly absorbed after oral administration,
bilastine relieves allergic symptoms within the hour.9,10,11
Its long lasting effectiveness allows the control of allergic
symptoms with just once-daily dosing.10,11

Bilastine provides rapid allergy relief


within one hour, with long-lasting
effectiveness that allows control of
allergic symptoms with once-daily dosing.
Bilastine clinical efficacy in the treatment of
allergic rhinitis and urticaria
The daily administration of bilastine 20 mg has been clinically
proven to significantly decrease nasal and non-nasal
symptoms of AR, alleviate AR-associated discomfort and
improve patients quality of life.12,13 Randomized, double-

Changes at day 14 (%)

Sneezing

-30

0
-40 -10
-50 -20

Runny nose
-38.3

-41

-60 -30
-70 -40

-80

Ocular redness

Bilastine 20 mg (n=226)

Nasal congestion

Tearing

Ocular redness

-35.3

-59.1
* -64.4
-41.2 *

-61.9 -59.5
* *
-42.3

-58.4 -57.4
* *

-63.7 -64.3
* *

Ocular itching

-41.2

-42.3

-60
-70

Nasal itching

-58.4 -57.4
* *
-38.3

-63.7 -64.3
* *
-41

-80 -50

Cetirizine 10 mg (n=227)

-59.1
* -64.4
*

-61.9 -59.5
* *

-50.6 -48.5
* *
-35.3

-51

-56.3
-65.3 -65.2

-67
-70.9
*
*
-51

-50.6 -48.5
* *

-56.3
-65.3 -65.2

-67
-70.9
*
*

*p < 0.001 vs. baseline; p < 0.001 for bilastine/cetirizine vs. placebo

Figure 2: Bilastine reduces urticaria symptoms14


0
-0.2
-0.4
-0.6
-0.8
-1

-1.2
-1.4
-1.6
-1.8
-2

-2.2
-2.4

0
-0.2
-0.4

-1.00

-1.01

-0.6
-0.8
-1
-1.2

-1.37*

-1.47*
-1.00

-1.01

-1.4
-1.6

Placebo (n=184)

-1.47*

-1.48*

-1.56*

-1.37*
Levocetirizine 5 mg (n=165)

-1.8

Bilastine 20 mg (n=173)

-1.56*

-1.48*

*p < 0.001 for bilastine and levocetirizine vs placebo; p = NS between bilastine and levocetirizine

-2

-2.2
blind, parallel-group,
multicenter
studies were performed
to Positron emission
tomography (PET) data indicate almost
Placebo (n=184)
Levocetirizine 5 mg (n=165)
Bilastine 20 mg (n=173)
examine the-2.4
efficacy and safety of bilastine 20 mg compared zero occupancy by bilastine of H1 receptors in the brain,
12,13
which is consistent with its lack of sedative effects.16 Even at
with placebo, cetirizine 10 mg and desloratadine 5 mg.
Data from 1,402 patients treated for 14 days indicated double the recommended dose of 20 mg, bilastine does not
that bilastine 20 mg was significantly more efficacious than impair psychomotor performance.17 Furthermore, a driving test
placebo and had an efficacy profile similar to that of cetirizine of subjects taking bilastine confirmed that neither single nor
repeated doses of bilastine 20 mg or 40 mg affected driving
and desloratadine (Figure 1).12,13
performance.18
Bilastine 20 mg is also clinically proven to be effective in
treating urticaria. In a randomized, double-blind, parallel- Bilastine is not only well-tolerated, it is also suitable for use by
group, multicenter study, 525 patients with chronic idiopathic many patient types. No dose adjustment is required in elderly
urticaria were treated for 28 days. Bilastine 20 mg reduced patients, nor in those with renal or hepatic impairment.19 As
patients total symptom score (which included pruritus severity, there is no interaction with CYP450 isoenzymes, it is unlikely
wheal number and maximum wheal size) (Figure 2), improved to be involved in drug interactions related to cytochrome
patients quality of life (as assessed by the Dermatology Life P450.15
Quality Index, DLQI) and decreased urticaria-associated
discomfort significantly more than placebo, and was as Conclusion
effective as levocetirizine 5 mg.14
Bilastine, a new, second-generation antihistamine, is an ideal
combination of high efficacy with a good safety and tolerability
Bilastine safety and tolerability profile
profile. It effectively and rapidly relieves symptoms of AR and
Data from clinical studies involving over 3,000 subjects urticaria, enabling a better quality of life for patients. It has a
treated with bilastine have demonstrated that bilastine has favorable safety profile and requires no dose adjustment for
a favorable safety and tolerability profile.15 In phase II and elderly patients or patients with renal or hepatic impairment.
phase III clinical trials of AR and chronic urticaria patients, the With these features, bilastine is poised to fulfill the need for
incidence of bilastine-related adverse events was the same an effective, non-sedating antihistamine for the treatment of
as that of placebo.15 Bilastine 20 mg is as well-tolerated as AR and urticaria.
desloratadine 5 mg, and the incidence of somnolence and
fatigue with bilastine is significantly lower than that with
Bilaxten is the trade name of bilastine in Singapore, Malaysia
cetirizine.12,13
and the Philippines.

Safety profile of bilastine, based on extensive


clinical studies:15
Minimize somnolence and fatigue
Limited penetration of the blood-brain barrier
No drug-drug interactions associated with cytochrome
P450
No dose adjustment in renal or hepatic impaired
patients
No clinically relevant cardiovascular effects
No anticholinergic effects

Sponsored as a service to the medical community by A. Menarini Asia-Pacific Holdings Pte Ltd.

References:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.

Bousquet J et al. Allergy 2008;63(Suppl. 86):8-160.


Zuberbier T et al. Allergy 2014;69(10):1275-9.
Maurer M et al. Allergy 2011;66:317-30.
Bousquet J et al. J Allergy Clin Immunol. 2009;124(3):428-33.
Katelaris CH et al. Am J Rhinol Allergy 2011;25 Suppl 1:S3-15.
Bousquet J et al. J Allergy Clin Immunol. 2010;126(5):926-38.
Corcstegui R et al. Drugs R D. 2005;6:371-84.
Corcstegui R et al. Drugs R D. 2006;7:219-31.
Jauregizar N et al. Clin Pharmacokinet. 2009;48:543-54.
Horak F et al. Inflamm Res. 2010;59:391-8.
Church MK. Inflamm Res. 2011;60:1107-12.
Kuna P et al. Clin Exp Allergy 2009;39:1338-47.
Bachert C et al. Allergy 2009;64:158-65.
Zuberbier T et al. Allergy 2010;65:516-28.
Church MK. Expert Opin Drug Saf. 2011;10:779-93.
Farr M et al. Br J Clin Pharmacol. 2014;78(5):970-980.
Garcia-Gea C et al. J Clin Psychopharmacol. 2008;28(6):675-85.
Conen S et al. J Psychopharmacol. 2011;25:1517-23.

REG/BIL/122014/005

There is an unmet need for treatment for AR and urticaria, as


uncontrolled symptoms impair patients quality of life, interfering
with activities and affecting many aspects of their everyday life,
ranging from sleep quality to social interactions.1,3 AR affects
at least 600 million people worldwide, and its prevalence
in Asia-Pacific has been increasing over the past 10 years,
causing significant socioeconomic cost to the region.4,5
However, about 20% of patients with severe persistent AR
still suffer from inadequately controlled symptoms.4 Similarly,
urticaria alone affects up to 25% of the total population at
least once in their lifetime, but current standard therapies fail
to control symptoms in over 50% of patients with chronic
spontaneous urticaria alone.3

Bilastine 20 mg (n=226)

SG-OGI-001mta

The need to improve treatment of allergic


rhinitis and urticaria

Placebo (n=225)

-20

Changes at day 14 (%)

Allergy symptoms, such as those caused by allergic rhinitis


(AR) and urticaria, pose a global health problem because of
their high prevalence, socioeconomic cost and impact on
quality of life. AR is clinically characterized by the presence of
rhinorrhea, sneezing, nasal itching and/or nasal obstruction,
while urticaria is characterized by the sudden appearance of
wheals and/or angioedema.1,2

-10

Mean change in symptom


score at day 28
Mean change in symptom
score at day 28

FAAAAI (MD, PhD, MSEE)


Professor for Medical Informatics and Deputy Chairman
Institute of Medical Statistics, Informatics and Epidemiology
University of Cologne, Germany

Cetirizine 10 mg (n=227)

Sneezing
Runny nose
Nasal itching
itching
Nasal congestion
Figure
1: Bilastine
effectively
relieves
nasal andOcular
ocular
allergic
symptoms12 Tearing
0

1 -31 Ja n ua ry 2 01 5

Co n fe r e n ce Cov e r ag e

43

IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting


2014, November 14-16, Taipei, Taiwan Chuah Su
Ping reports

Fracture risk in diabetics


underestimated

he potential for fracture in patients with diabetes may be underestimated, as some of

the major fracture assessment tools that are avail-

The investigators concluded that the FRAX

able do not take into account diabetes as a risk

underestimated observed major osteoporotic

factor.

and hip fracture risk in diabetics (adjusted for

Fractures are a common complication of

competing mortality), thus suggesting that

diabetes, with common fracture sites including

diabetes might be considered for inclusion in

the hip, wrist and spine, said Dr. Jung Fu Chen,

future iterations of FRAX. However, more re-

of the division of endocrinology and metabolism

search is required in collecting new population

(Osteoporosis Clinic), Chang Gung Memorial

cohorts worldwide before this risk factor can be

Hospital, Kaohsiung, Taipei. However, despite

included in the FRAX, Chen opined.

the metabolic abnormalities of diabetes which

More recently, a Taiwanese study evaluated

do affect bone metabolism, structure and bone

fracture risk and post-fracture mortality in pa-

mineral density (BMD), the association between

tients with diabetes. Using data obtained from

increased fracture risk in individuals with type 1

Taiwans National Health Insurance Database,

and 2 diabetes continues to be debated.

they identified 32,471 adults with newly diag-

Chen noted that the current algorithm of the

nosed diabetes from 2000 to 2003; and fracture

WHO fracture risk assessment tool (FRAX)

events from 2000 to 2008 from medical claims.

does not include diabetes as a risk factor. In

Based on 652,530 person-years of follow-

2012, researchers reported that diabetes was

up, they noted that the incidences of fracture

a significant predictor of subsequent major

for people with and without diabetes were 24.2

osteoporotic fracture after controlling for age,

and 17.1 per 1,000 person-years, respectively

sex, medication use and FRAX risk factors in-

(p<0.0001). Compared with people without di-

cluding BMD. Diabetes, they reported, was

abetes, diabetics face a higher risk of fracture

also associated with significantly higher risk

(HR, 1.66, 95% CI, 1.60-1.72). The study also

for hip fractures (p<0.001). [J Bone Miner Res

found that the odds ratios of post-fracture deep

2012;27:301-8]

wound infection, septicemia, and mortality as-

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

44

sociated with diabetes were 1.34 (95% CI, 1.06-

from the American Diabetes Association for as-

1.71), 1.42 (95% CI, 1.23-1.64) and 1.27 (95%

sessment of fracture risk and implementation of

CI, 1.02-1.60), respectively, said Chen. [Diabe-

prevention strategies in persons with diabetes,

tes Care 2014;37:2246-52]

particularly those with poor glucose control.

Similarly, investigators from the Atheroscle-

[Diabetes Care 2013;36:1153-8]

rosis Risk in Communities (ARIC) Study a US-

With the ever-growing population of diabet-

based study with patients recruited from four

ics in Asia, coupled with an increasing aging

US communities had reported that diagnosed

population, a multidisciplinary team approach

diabetes was significantly and independently

which includes bone care is very crucial for the

associated with an increased risk of fracture.

integrated management of diabetic patients,

The ARIC study supports recommendations

concluded Chen.

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

45

IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting 2014, November 1416, Taipei, Taiwan Chuah Su Ping reports

Osteoporotic fractures in men


highlights from the MrOS study

ractures resulting from osteoporosis are

said Orwoll. [J Bone Miner Res 2006;21:1550-

a major healthcare challenge in men, yet

6] More recently, another paper from the MrOS

the rate of detection and management of male

study noted that men with accelerated femo-

osteoporosis lags well behind that in women,

ral neck BMD loss had an increased risk of hip

according to an expert.

and other non-spine fractures. [J Bone Miner

The residual lifetime risk of experiencing

Res 2012;27:2179-88]

an osteoporotic fracture in men 50 years old

While the MrOS study has provided further

and above is estimated to be approximately

understanding of osteoporosis fractures in

27 percent. [Osteoporosis Int 2001;12:124-10]

men, it did also raise questions. [One] study,

In comparison, the risk of developing prostate

for example, raised the question of whether

cancer in men over the age of 50 has been cal-

or not men with low-to-normal BMD (not yet

culated at around 11 percent. [Cancer Epide-

in the range requiring treatment) should have

miol Biomarkers Prev 1997;6:763-8]

a repeat [BMD] measurement in 2-to-3 years,

The Osteoporotic Fractures in Men (MrOS)

and whether or not to treat men with the great-

Study is a prospective cohort study designed

est rate of bone loss earlier, said Orwoll. The

to examine the extent to which fracture risk is

researchers concluded that further research

related to bone mass, bone geometry, lifestyle,

was still needed in order to determine if repeat

anthropometric and neuromuscular measures,

BMD testing and subsequent treatment in such

and fall propensity, as well as to determine how

a population would be cost effective. [J Bone

fractures affect quality of life in men, said Dr.

Miner Res 2012;27:2179-88]

Eric Orwoll, professor of medicine and direc-

Orwoll also highlighted a MrOS substudy

tor, of the Bone and Mineral Clinic at Oregon

which showed an association between poor

Health and Science University, Portland, Ore-

physical performance and the likelihood of in-

gon, US. [Contemp Clin Trials 2005;26:569-85]

cident vertebral fractures. The investigators

To date, the MrOS study has helped estab-

concluded that men who performed poorly on

lish that although women have a higher risk of

several tests chair stand, walking speed, leg

fracture, the association between bone min-

power, narrow walk and grip strength had

eral density (BMD) and fracture risk is clearly

twice the risk of radiographic vertebral frac-

evident in men, and similar to that in women,

tures over time compared with men who did

1 -31 JA n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

46

not perform poorly on any test, said Orwoll. [J

portant outcomes such as fracture, and

Bone Miner Res 2014;29:2101-8]

physical disability, said Orwoll. Using high

The MrOS study is still ongoing, and next

resolution micro-computed tomographic im-

phase aims to provide further understand-

aging, our goal is to further assess the rela-

ing of the trajectories of change in muscu-

tionship between bone microstructure and

loskeletal health, and how they affect im-

fracture risk.

READ JPOG ANYTIME, ANYWHERE.


Download the digital edition today at www.jpog.com

All night...

All day...

Cardio protection
Amlodipine

The first line treatment in hypertension:


Smooth and prolonged activity
Proven safe in elderly patients(1)
Compatible with -blockers and ACE inhibitors
Provides more protection against stroke and MI
than other antihypertensive drugs(2)
Once daily
References:

1) Ji-Guang Wang et al. Hypertension 2007; 50:181-188.


2) Pascual J. Curr Med Res 2000; 16(1):33-36.

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1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

48

19th Congress of Asian Pacific Society of Respirology (APSR), November 1316, Bali, Indonesia

Attitude determines outcome,


treatment strategy in asthma
Pank Jit Sin

asthma patients through personalized solutions


instead of a one-size-fits-all approach.

he findings of the Recognise Asthma and

Wang went on to describe each clusters

Link to Symptoms and Experience (RE-

character profile, with the Well Adjusted ones

ALISE) survey reveals that asthma patients

being able to cope well with their asthma and

can be segmented into distinct and actionable

being minimally impacted in their daily lives,

groups based on their attitude towards asthma.

both emotionally and functionally. Additionally,

Dr. Aileen David-Wang, clinical associate pro-

they are happy to go along with their doctors

fessor, University of the Philippines, Philippine

advice and have no problem using their inhaler

General Hospital, said the survey was aimed at

a reflection of their carefree attitude and lower

identifying distinct and explicit patient clusters

stress levels.

in Asia, defined by their differing attitudes, ad-

The Rejectors are patients who have to come

herence, educational needs and other impor-

to terms with the emotional burden of living with

tant attributes.

asthma, and their asthma is generally well con-

The survey assigned patients into one of

trolled. The refusal to accept their disease state

five clusters Well Adjusted; Rejector; Lost;

is reflected in their tendency to deprioritize their

Endurer; and Worrier. The attitudes of patients

health. This cluster is also particularly conscious

could confidently determine their asthma con-

about using the inhaler in public.

trol based on the Global Initiative for Asthma

Those in the Lost cluster generally have

(GINA)-defined criteria. The Well Adjusted and

a high level of stress and anxiety about their

Rejector clusters typically had a high level of

poorly controlled asthma. This leads to a rejec-

asthma control. The Lost and Endurer clusters

tion of their asthma status, their doctor and their

experienced low asthma control, while the Wor-

inhaler, said Wang. The Lost tend to be evasive

riers had the lowest control of asthma. Wang

and avoid thinking about their health problems

said each cluster has different information

[asthma], despite being emotionally and func-

needs and requires a tailored management ap-

tionally affected by it. However, they frequently

proach.

seek information regarding asthma, suggesting

Through proper matching of patients attitudinal cluster, doctors can optimally manage

that they have unanswered questions and are at


a loss for answers.

1 -31 JA n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

49

Meanwhile, the Endurers are those who have

The cluster most troubled by their asthma

resigned themselves to the fact that they have

are the Worriers. To them, asthma is a constant

asthma and that they have no control over the

bother and always on their mind. Worriers are

disease. Even though their level of confidence

able to come to terms with being labeled as

in managing their asthma is low, the situation

asthmatic and acknowledge the seriousness of

doesnt impact their daily life, emotionally or

asthma, but live with a high level of stress and

functionally. The Endurers are fine with using

anxiety over the disease. This is reflected in the

their inhaler [in public] and are less interested

high level of concern they have regarding their

in finding out more about asthma compared to

asthma and the high frequency of information

other poorly controlled clusters.

seeking, noted Wang.

1 -31 Ja n ua ry 2 01 5

Co n fe r e n ce Cov e r ag e

50

19th Congress of Asian Pacific Society of Respirology (APSR), November 1316, Bali, Indonesia

Harm from man-made fibers unclear


Pank Jit Sin

[Available at http://monographs.iarc.fr/ENG/
Monographs/vol81/mono81.pdf Accessed on

an-made fibers are defined as those

9 December]

whose chemical composition, structure

Faisal noted that cancer is now a leading

and properties are significantly modified during

cause of death, with 12.7 million new cases and

the manufacturing process. These are spun and

7.6 million deaths in 2008. The World Health

woven into a number of consumer and industrial

Organization (WHO) attributes 19 percent of all

products such as rayon, nylon and dacron. On

cancers as being caused by the environment,

the other hand, natural fibers are composed of

including at work, with about 1.3 million deaths

biologically produced compounds such as cel-

each year.

lulose and protein. Such fibers emerge from the

Of this number, one in 10 lung cancer deaths

manufacturing process in a relatively unaltered

are closely related to risks in the workplace. Ac-

state, for example, silk and cotton.

cording to the WHO, lung cancer, mesothelioma

Speaking on the topic of man-made fibers

and bladder cancer are among the most com-

and the relationship with cancer, Professor Fais-

mon types of occupational cancers. For cancers

al Yunus, senior lecturer, Department of Pulm-

of the lung, arsenic, asbestos, coal, engine ex-

onology and Respiratory Medicine, Faculty of

haust and chromium compounds are linked to

Medicine, University of Indonesia, said the fibers

carcinogenicity in humans. Additionally, crystal-

studied were made from various components

line silica dust, soot, tobacco smoke and out-

and largely used in the electrical and insulation

door particulates are also proven lung carcino-

industry, especially wool and filament types.

gens.

The International Agency for Research on

However, there is insufficient evidence from

Cancer (IARC) has stated that there is inade-

both animal and human studies for carcino-

quate evidence of carcinogenic effects of glass

genicity of fibers such as continuous glass

wool, continuous glass filament rock wool, slag

filament, alkaline earth silicate wool, high-

wool and refractory ceramic fibers in humans.

alumina, and low-silica wools. Data from ani-

However, experimental evidence abounds for

mal studies indicating that man-made vitreous

carcinogenicity of special-purpose glass fibers

fibers are potentially carcinogenic are also

such as E-glass and refractory ceramic fibers.

inconclusive.

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

51

19th Congress of Asian Pacific Society of Respirology (APSR), November 1316, Bali, Indonesia

Natural disasters can affect lung health


ble diseases, about 180,000, occurred within

Radha Chitale

the first 12 weeks following the disaster.


atural disasters have significant direct

Large natural disasters can cause existing

and indirect effects on lung health and

healthcare services to break down resulting in

can have long-term repercussions, particularly

a lack of medical care for routine pulmonary

in the Asia-Pacific region, where 80 percent of

events. Healthcare workers are also at risk for

the worlds natural disasters in the 20 and 21

physical injury, infection, and may be worried

th

st

centuries have occurred.

about the safety of their own families.

Earthquakes, tsunamis, volcano eruptions

Patients with existing pulmonary disease

and typhoons can be violent and dirty, expos-

are at risk during natural disasters if there

ing people in the area to harmful particulate

are disruptions to power for oxygen delivery,

matter and microbes. Efforts to gather people

routine medicines for asthma or chronic ob-

together for care immediately after a disaster

structive pulmonary disorder, or if there is no

can lead to further harm.

physiotherapy or other services for people with

Respiratory infectious diseases are the

chronic diseases like cystic fibrosis.

main problem, said Dr. Bruce Robinson of the

To be prepared, Robinson recommended

University of Western Australia and director of

backup power sources, medication stores, and

the National Centre for Asbestos Diseases Re-

adequate transport plans to move patients to

search in Perth, Australia.

better facilities. [Respirology 2011;16:386-95]

Following a tsunami, for example, there is


water everywhere creating lots of places for
mosquitoes the disease vectors to breed.

There are four main direct effects of disasters on the lungs.


Small particles of smoke or toxic gases from

Crowding following a disaster can lead to

fires or volcanic emissions can be inhaled, and

rapid infection spread due to exposure. Dis-

if they are hot the lungs can burn, become

eases such as measles, acute lower respira-

leaky, and be poisoned by carbon monoxide.

tory tract infection, and tuberculosis all of

The 1997 haze fires in Indonesia caused

which can be fatal without prompt, appropriate

over 500 haze-related deaths in 3 months as

treatment can spread quickly.

well as 300,000 cases of asthma, 50,000 cases

Following the 2004 earthquake and tsunami


that hit parts of Thailand, more than half (62
percent) of the consultations for communica-

of bronchitis, and 1.5 million respiratory infections, Robinson said.


Aspirating water can introduce water-borne

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

52

pathogens to the lungs. Direct trauma to the

engage with the psychological trauma af-

chest when buildings fall down can result in rib

ter a disaster... What Ive found is that its

fractures or diaphragm rupture.

very important to talk to the patients be-

Psychological trauma following a natural

cause no one else is talking to them, he

disaster can also result in physical manifesta-

said. Particularly when a mass group is af-

tions that need to be managed, Robinson said.

fected, it becomes important for the doctor to

As a chest physician, its important to

engage.

READ JPOG ANYTIME, ANYWHERE.


Download the digital edition today at www.jpog.com

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EGb 761 proven effective for NPS symptoms in


Alzheimers disease
Ginkgo biloba has been shown to improve cognitive as well as neuropsychiatric symptoms (NPS) in patients with Alzheimers disease (AD) and
mixed dementia. During a Schwabe-sponsored symposium last 20 October 2014 held at the University of Malaya in Malaysia, Professor Serge
Gauthier of the McGill Centre for Studies in Aging in Quebec, Canada, and Dr Robert Hoerr of the Dr Willmar Schwabe GmbH & Co. KG in
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Neuropsychiatric symptoms in mild cognitive impairment and dementia


Professor Serge Gauthier
McGill Centre for Studies in Aging
Verdun, Quebec
Canada

Alzheimers disease and dementia


AD has been recognised for over a century, with the first
documentation of the disease attributed to Alois Alzheimer
in 1902, wherein he first described NPS and cognitive
impairment in a patient who appeared to have AD.1 Presently,
AD accounts for majority of dementia cases, followed by
mixed type of dementia.2 The natural course of AD involves
cognitive symptoms in early diagnosis, which progresses to
loss of functional independence and behavioural problems
that may necessitate full-time nursing care.

AD frequently overlaps with other types of neurological


pathologies, especially in patients over 80 years of age. A
study shows that mixed pathologies occur in almost half of
cases with probable AD and in almost 20% of patients with
mild cognitive impairment (MCI).3 Mixed pathologies were
also found to involve AD with macroscopic infarcts or AD
with neocortical Lewy body disease.

Biological treatment of AD
Medical treatments for AD and other dementias are based
on the latest guidelines developed by the World Federation
of Societies of Biological Psychiatry (WFSBP).4 According to
the guidelines, symptomatic treatment of AD and vascular
dementia (VaD) include cholinesterase inhibitors (CIs), EGb
761 (Ginkgo biloba extract) and N-Methyl-D-aspartate
(NMDA) receptor antagonists (e.g. memantine).

The guidelines included studies that had sample population


of at least 100 patients, with diagnosis of AD or AD with
cerebrovascular disease (CVD) or VaD in accordance with
internationally accepted criteria, using assessments in at
least two of three typical domains required by the US Food
and Drug Administration and European Medicines Agency
guidelines (eg, activities of daily living, cognition, global
rating), and with treatment duration of at least 20 weeks.
Based on seven trials involving a total of 2,625 patients,
Ginkgo biloba has been shown to be well tolerated and
superior to placebo in the treatment of patients with
dementia. According to the WFSBP guidelines, intake of 240
mg daily doses and the presence of NPS were associated
with better response in AD/dementia patients with NPS.
EGb 761 is, therefore, an evidence-based treatment option
in patients with AD, with or without CVD.

Outcome improvements in Alzheimers disease treatment


GINDEM-NP Study

Head of Geriatrics/CNS
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Germany

GINDEM-NP, a randomised, double-blind trial involving 400


patients, showed that EGb 761 (240 mg/day) was superior to
placebo with respect to primary and all secondary outcome
variables.9 The study included patients with probable AD or
possible mixed dementia with AD who scored 9 to 23 on the
Short Cognitive Performance Test (Syndrom-Kurztest, SKT,
primary outcome) and at least 5 on the Neuropsychiatric
Inventory (NPI). Results show that composite score (ie,
frequency x severity) and the mean caregiver distress score
of the NPI dropped from 21.3 to 14.7 and 13.5 to 8.7,
respectively in the EGb 761 group, but increased from 21.6
to 24.1 and 13.4 to 13.9, respectively in the placebo group
(p<0.001). The largest differences proving superiority of EGb
761 were scores in apathy/indifference, anxiety, irritability,
depression and sleep/night-time behaviour (Figure 1).

Neuropsychiatric symptoms in AD
A considerable number of patients with dementia have
NPS, with one study reporting an incidence rate as high
as 96%.5 Thus, NPS is now considered as a key outcome of
interest in the clinical evaluation of anti-dementia drugs.
In 2011, the National Institute on AgingAlzheimers
Association has also recognised that cognitive or behavioural
impairment may involve changes in personality, behaviour
or comportment. Symptoms may include uncharacteristic
mood fluctuations such as agitation, impaired motivation,
initiative or apathy, among others.6
In 2013, the DSM-V criteria for probable major
neurocognitive disorder does not explicitly include NPS
in the core criteria, but the symptoms are indicated by
specifiers and recognised at least as part of the syndrome.7

Tebonin EGb 761 for NPS


EGb 761 is a well-researched herbal product for MCI and
AD, particularly in the treatment of NPS. The dry extract
from Ginkgo biloba leaves is adjusted to 22% to 27% Ginkgo
flavonoids, with 5% to 7% terpene lactones consisting of
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EGb 761s quantification is achieved by a strict in-process
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high batch-to-batch consistency.
Other Ginkgo products may have entirely different
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products have been found to have substantial disparity in
dissolution rates and contain undesirable substances.8
Unlike in other anti-dementia drugs that have no reported
data specific to NPS, various trials have demonstrated that
EGb 761 is effective specifically in the symptomatic treatment
of NPS in amnestic MCI, as well as in AD and mixed dementia.

GOTADAY study
The multicentre GOTADAY trial confirmed the efficacy and
safety of a once-daily formulation of EGb 761 in treating
dementia with neuropsychiatric features.10 The 410 out
patients with mild to moderate dementia scoring between
9 and 23 on the SKT cognitive battery test and at least 5 on

the NPI were treated with either 240-mg EGb 761 or placebo
once daily for 24 weeks. Patients in the EGb 761 group
improved by -1.4 (95% CI, -1.8; -1.0) points on the SKT and by
3.2 (-4.0; -2.3) on the NPI total score, whereas those receiving
placebo (n=202) deteriorated by +0.3 (-0.1; 0.7) on the SKT
and did not change on the NPI total score (-0.9; 0.9).

GIMCIPlus study
The
randomised,
placebo-controlled,
double-blind,
multicentre GIMCIPlus trial explored the effects of EGb
761 on NPS and cognition in patients with amnestic MCI
according to international consensus criteria.11 A total of
160 patients who scored at least 6 on NPI were enrolled to
receive either 240 mg EGb 761 daily or placebo for 24 weeks.
Results showed that the NPI composite score decreased by
a mean of 7.04.5 points in the EGb 761-treated group,
and by 5.55.2 points in the placebo group (p=0.001; Figure
2). The study concluded that EGb 761 improves NPS and
cognitive performance in patients with amnestic MCI.

Figure 2. GIMCIPlus: NPI response rates11


70
60
Response Rates (%)

Dr Robert Hoerr

Figure 1. GINDEM-NP: Change from baseline


in NPI composite scores by item9
-2 -1.5

-1 -0.5

0.5

1.5

50

EGb 761
Placebo
p <0.01

40
30
20
10

Delusions

Hallucinations
Agitation/Aggression
Depression/Dysphoria
Anxiety
Elation/Euphoria
Apathy/Indifference
Disinhibition
Irritability/Lability
Aberrant Motor Behaviour
Sleep/Nighttime Behaviour
Appetite/Eating

KEY MESSAGES
Tebonin (EGb 761) improves the cognitive functions and NPS in dementia and MCI patients.
Tebonin (EGb 761) is most effective in dementia patients with higher NPS burden at baseline.

Conclusions
AD is the most common type of dementia, with a substantial
number of cases having associated NPS. Various studies have
proven that EGb 761 improves NPS in patients with AD and
those with MCI. These studies have also shown that there is
greater improvement with EGb 761 in patients who have
higher burden of NPS at baseline.
The SKT contains nine subtests that evaluate memory and attention.
NPI examines at least 10 sub-domains of behavioural functioning such as delusions,
hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition,
irritability/lability, aberrant motor activity, appetite, night-time disturbances.

REFERENCES: 1. Vishal S, Sourabh A, Harkirat S. J Med Biogr 2011;19:32-3. 2. Law


A, Gauthier S, Quirion R. Brain Res Rev 2001;35:73-96. 3. Schneider JA, Arvanitakis Z,
Leurgans SE, et al. Ann Neurol 2009;66:200-8. 4. Ihl R, Frlich L, Winblad B, et al. World J
Biol Psychia 2011;12:2-32. 5. Petrovic M, Hurt D, Collins D, et al. Acta Clin Belg 2007;62:42632. 6. McKhann GM, Knopman DS, Chertkow H, et al. Alzheimers Dement 2011;7:263-9.
7. American Psychiatric Association. Diagnostic and statistical manual of mental
disorders, 5th ed. Washington, DC, 2013. 8. Kressman S. J Pharm Pharmacol 2002;54:6619. 9. Scripnikov A, Khomenko A, Napryeyenko O. Wien Med Wochenschr 2007;157:295300. 10. Ihl R, Bachinskaya N, Korczyn AD, et al. Int J Geriatr Psychiatry 2011;26:1186-94.
11. Gavrilova SI, Preuss UW, Wong JWM. Int J Geriatr Psychiatry 2014;29:1087-95.

Sponsored as a service to the medical profession by Schwabe and LF Asia.


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Memory loss?
As we age, brain activity slows down and this may lead
to memory loss. Serious medical conditions such as
dementia robs an individual not just of memories but
their normal day-to-day routine.

1 -31 Ja n ua ry 2 01 5

CO N F E R E N C E COV E RAG E

55

19th Congress of Asian Pacific Society of Respirology (APSR), November 1316, Bali, Indonesia

Air pollution a leading preventable


cause of death worldwide
Chuah Su Ping

it is linked to at least 12,000 deaths. This event


was significant as it led to increased public

ir pollution is one of the major causes of

awareness, government regulation and environ-

mortality globally.

mental research, he said. The level of pollution

Ambient air pollution was estimated to have

noted in the 1952 smog in London, can now be

caused an excess of 3.7 million premature

seen in key cities in China, in particular Beijing,

deaths in 2012, with 88 percent of these excess

and India.

deaths having occurred in low- and middle-in-

Indoor air pollution is also a major concern.

come countries, said Professor Emeritus Nor-

Up to 3 billion people rely on the burning of bio-

bert Berend, head of Respiratory Research at

mass fuels indoors as a source of heating or to

the George Institute for Global Health, Sydney,

cook, and this has been linked to approximately

Australia. He noted that the causes include rapid

4.3 million deaths yearly. Of that figure, 1.69 mil-

industrialization, increased motor vehicle traffic

lion deaths are from Southeast Asia, and 1.62

and the use of cheap coal as a source of power.

million are from the Western Pacific region,

The many effects of air pollution can be di-

said Berend. Worldwide, he noted, the use of

vided into acute and chronic effects. Acute ef-

biomass fuels is especially high in urban slum

fects include respiratory symptoms, cardiovas-

populations.

cular events, hospitalizations and mortality, and

As healthcare practitioners, what we need

these are more pronounced in people with un-

to do now is to continue to advocate for lung

derlying respiratory or cardiovascular diseases.

health to the public, government health depart-

Chronic effects range from reduction of lung

ments as well as international agencies. Whilst

growth in children and adolescents, reduced

it is important that we continue the anti-smok-

lung function in adults and lung cancer, said

ing lobby, we must also demand an upgrading

Berend.

of international air quality standards as well as

Berend highlighted the Great Smog of 1952,

adherence to these standards. We also need

which was a severe air-pollution event that af-

to push for increased research funding from

fected London from December 5 to 8 in 1952.

individuals, national and international respira-

The Great Smog is known to be the worst air

tory societies to improve the field of respiratory

pollution to have ever occurred in the UK, and

health.

1 -31 Ja n ua ry 2 01 5

I n te r n atio n a l

57

Shield heart, hold breath during


radiotherapy
Dr. Joslyn Ngu

adiation exposure to the heart is lessened


if a woman holds her breath during radio-

therapy for left-sided breast cancer, reveals a


study.
Women with breast cancer on their left side
have a higher risk of heart disease post radiotherapy. This is because it is difficult to protect

their breath during radiotherapy until therapeu-

the heart from radiation exposure and at the

tic dose was achieved. The researchers found

same time, ensure that an appropriate amount

that patients who were able to hold their breath

of radiation is delivered to the left breast. The

over the course of treatment had a 90 percent

study, which is the largest prospective study of

disease free survival and 96 percent overall sur-

its kind, found that if patients held their breath

vival. The median reduction in dose of radiation

during radiotherapy, radiation exposure to the

to the heart was 62 percent.

heart was reduced by more than half.

We offer breast cancer treatment together

The breath holding method works by allowing

with the breath-holding technique in our center

practitioners an opportunity to monitor patients

because it helps protect the heart during radio-

breath for the position that moves the heart out

therapy, said senior author and Associate Pro-

of the range of the radiation beam.

fessor Rani Anne, of the Department of Radia-

After surgery, radiation therapy is usually

tion Oncology, Thomas Jefferson University, US.

given to patients with breast cancer as a part

Neoteric studies have shown that women

of first-line therapy, said first author Dr. Harriet

with left-sided breast cancer have an elevated

Eldredge-Hindy, chief resident of the Depart-

risk of heart disease. The risk rises in correspon-

ment of Radiation Oncology, Thomas Jefferson

dence with the dose of radiation the heart is ex-

University, US. We wanted to assess how ef-

posed to during radiotherapy. Among the meth-

fective breath-holding could be in shielding the

ods that have been deployed to lessen radiation

heart from extraneous radiation exposure during

exposure to the heart are prone positioning (the

treatment of cancer in the left breast.

patient lies flat on the stomach on a bed that ex-

The study involved 81 women who were

poses only the left breast), intensity-modulated

monitored for 8 years post therapy. All of them

radiation therapy (IMRT) and accelerated partial

were breast cancer patients who repeatedly held

breast irradiation.

A
20-22

ug

15
ust 20

ff

Ra

e
r
o
ap

Sing

nv

Co
y
t
i
C
les

tre

Cen
n
o
i
t
n
e

The Synthesis of
Evidence, Experience,
and Choice in
Womens Health
Call for Abstracts, Registration,
and Programme at
www.sicog2015.com

1 -31 Ja n ua ry 2 01 5

I NT E RNAT I O NAL

59

SBRT plus erlotinib improve survival


in lung cancer
Dr. Joslyn Ngu

study shows that a combination therapy


of stereotactic body radiation therapy

(SBRT) and erlotinib is able to increase the sur-

vival rates for patients with stage 4 non-small


cell lung cancer (NSCLC), compared to treatment with erlotinib alone.
If a patient is given erlotinib, a type of chemotherapy, the overall survival time is merely

sure of adjacent healthy tissues and organs,

six to nine months. When erlotinib was given

said Professor Robert Timmerman, director of

together with SBRT, the overall survival dura-

clinical research and image-guided stereotac-

tion increased to 20 months. On top of that,

tic radiation therapy, Department of Radiation

for similarly chosen lung cancer patients, the

Oncology, UT Southwestern Medical Center,

progression free survival time is improved from

US.

two to four months (erlotinib only) to nearly 15


months (combination therapy).

There have been advancements in technology over the last few years. The advancements

The study, a phase 2 clinical trial, recruited

have given us new treatment options and we

24 patients with stage 4 NSCLC. All the partici-

can now reconsider administrating radiation

pants had NSCLC which continued to spread

together with chemotherapy, surgery and oth-

in spite of initial treatment, and were given the

er systemic therapies, said Timmerman, who

prognosis of poor survival rates. For these pa-

was the lead investigator in various national

tients, SBRT is not a common treatment mo-

studies designed to assess the safety and ef-

dality, said first author Assistant Professor

ficacy of SBRT in treating lung, liver, spine and

Puneeth Iyengar, of the Department of Radia-

prostate cancer.

tion Oncology, UT Southwestern Medical Center, US.

According to the National Cancer Institute,


an estimated total of 224,210 men and women

SBRT is a state-of-the-art technique that is

were diagnosed with lung cancer in 2014. About

able to send high doses of radiotherapy from

85 percent of lung cancer cases were diag-

multiple directions to small and well-defined tu-

nosed as NSCLC. From 2004 to 2010, five year

mors. It enables radiotherapy to be delivered

relative survival rates for lung cancer remained

directly to the tumors and minimizes the expo-

low at a mere 17 percent.

1 -31 Ja n ua ry 2 01 5

h u mor

61

I finally received your test results dear, but


before l let you read it, l would like you to sign
something for me!

Theres nothing wrong in trying to blend in,


but why must you always mimic the behavior of
others?

Any previous experience?

With medical students, the only way for them to


learn, is to let them make their own mistakes!

As far as l know he didnt


die of anything. He was a
hypochondriac!

Have you been putting on


weight?

Yes Doctor Manolete, youre


right. Its probably the full
moon!

1 -31 Ja n ua ry 2 01 5

C A L E N DAR

63

ANNOUNCEMENT
London College of Clinical Hypnosis and Academy of
Family Physicians Malaysia
Certificate in Clinical Hypnosis (UK University
accreditation + CME)
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Start : 31st January 2015
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2015 Rehabtech Asia

26/3 to 28/3; Singapore


Info : Sia Chen Wei
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Treatment of Hypertension,
Dyslipidemia and Diabetes
Mellitus
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World Cornea Congress VII
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15/4 to 17/4; San Diego, US
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16/4 to 18/4; Vienna, Austria


Info : Secretariat
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21/4 to 25/4; Cape Town,
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1 -31 Ja n ua ry 2 01 5

33rd Annual Meeting of


The European Society
for Paediatric Infectious
Diseases
12/5 to 16/5; Leipzig, Germany
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Fex : +41 22 908 9140
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m
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ASCO 2015 Annual Meeting
29/5 to 2/6; Chicago, US
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International Medical
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Arokiasamy;
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AOCOG 2015
24th Asian and Oceanic
Congress of Obstetrics and
Gynecology
3/6 to 6/6; Kuching
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50th International Liver


Congress 2015
22/4 to 26/4; Vienna, Austria
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Tel : (+41) 0 22 807 03 60
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World Glaucoma Congress


2015
6/6 to 9/6; Hong Kong
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Email : wgc-2015-reg@mci-
group.com
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2015 Eurospine
23/4 to 25/4; Copenhagen,
Denmark
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6th Congress of the


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Societies of Asia Oceania
(FIMSA2015)
30/6 to 3/7; Singapore
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C A L E N DAR

International Diabetes
Federation World Diabetes
Congress 2015
30/11 to 4/12; Vancouver,
Canada
Tel : (32) 2538 5511
Fax : (32) 2538 5114

64

Fexofin
Fexofin

Fast Relief
of Allergies

Onc
e
ily
Da

Non-sedative 2nd generation


antihistamine1
Does not cause cognitive or
psychomotor impairment2
Free from Cardiac adverse effects1
Effective and safe in respiratory
and dermatological allergies2,3

References:
(1) Meeves SG. et al. J Allergy Clin Immunol, 2003 Oct;
112 (4 suppl) S69-S77.
(2) Hiroyuki Kamei et al. Arch Dermatol Res (2012)
304:263272.
(3) Van Cauwenberge P, Juniper EF. Clin Exp Allergy,
2000 Jun;30(6):891-9.

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PP17111/12/2012 (031349) ISSN 1608-5086

Dato Dr. Ravindran Jegasothy


Medical Faculty, MAHSA University
Dermatology

Dr. Steven KW Chow


Pantai Medical Centre
Genito-Urinary

Dr. Doshi Hemendra Kumar


Medicine Klinik Kulit & Kelamin Shriji
M ed i c i n e R a d i o l o g y

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FRCR (UK)
University Malaya Medical Centre
O r th o ped i c & S p i n e S u r ge r y

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iHEAL Medical Centre