1. IBD on the rise in Asia,
most cases reported
in China
FORUM
Alcohol
in all policies
CONFERENCE
Novel therapeutic
interventions
for gastroparesis
CONFERENCE
Fracture risk
in diabetics
underestimated
CONFERENCE
Involve family
physicians in
community
palliative care,
say experts
JANUARY 2015
2. JANUARY 2015 2
ELVIRA MANZANO
There has been a progressive increase in
the incidence and prevalence of inflamma-
tory bowel disease (IBD) in Asia, characterized
by complicated disease behavior and signifi-
cant morbidity, says an expert at the recent Asia
Pacific Digestive Week conference held in Bali,
Indonesia.
“IBD has been traditionally known as a dis-
ease of the West and is relatively rare in Asia.
However, time trend studies from Japan, Korea
and Hong Kong have collectively shown a two-
to-three fold increase in the incidence and preva-
lence of IBD in the past 10 years,” said Professor
Siew Chien Ng from the Department of Medicine
and Therapeutics, Chinese University of Hong
Kong in Hong Kong.
In the first large scale population-based
study of IBD involving seven countries in Asia
(China, Hong Kong, Macau, Thailand, Malay-
sia, Singapore, Sri Lanka) and Australia, the
incidence of IBD varied from 0.54 to 3.44 per
100,000 individuals. China had the highest in-
cidence of IBD at 3.44 per 100,000. Ulcerative
colitis (UC) was more prevalent than Crohn’s
disease (CD), although the incidence of CD was
rapidly increasing in certain areas. [Gastroen-
terol 2013;145:158-165]
“Although family history of IBD was less com-
mon in Asia – as were extra-intestinal manifesta-
tions – complicated CD [penetrating, stricturing
IBD on the rise in Asia, most cases
reported in China
or perianal disease] was more common in Asia
than in the West,” said Ng.
In Hong Kong, for example, a study showed
the rate of perianal disease was 29.2 percent com-
pared with 15.8 percent in Australia (p=0.001). [J
Gastroenterol Hepatol 2012; 27:1266-1280]
“These changes may have been due to our
increased contact with the West, westernization
of diet, improved hygiene, increasing antibiotic
use, immune dysregulation and changes in the
gut microbiota,” Ng said. Asian patients with
CD have altered microbiota compared with their
Caucasian counterparts. Mucosa-associated mi-
crobiota in IBD may also differ geographically.
In a more recent population-based case-con-
trol study in Asia, where Ng was the principal in-
vestigator, breastfeeding, having pets and better
sanitary conditions were shown to be protective
of IBD, suggesting that childhood environment
plays an important role in modulating disease
development. [Gut 2014; pii: gutjnl-2014-307410.
doi: 10.1136/gutjnl-2014-307410]
The results, Ng said, highlight the importance
of childhood immunological, hygiene and dietary
3. JANUARY 2015 3
factors in the pathogenesis of IBD, suggesting
that markers of altered intestinal microbiota may
modulate risk of IBD later in life.
There are also differences in the genetic
mutations of IBD between Asians and Cauca-
sians, which may impact the development of
IBD, added Ng. NOD2 and autophagy variants
(ATG 16L1 and IL 23) are not associated with
CD in Asians, but TNF-SF15 polymorphisms are
strongly associated with CD.
“Understanding of the genetic variation and
mutations [of IBD] will help us to identify bio-
logical pathways causing the disease and to
discover better drugs for patients. More stud-
ies are warranted to determine the critical etio-
logic factors for IBD,” Ng said.
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4. JANUARY 2015 4
Linagliptin plus metformin combo
safe and effective in Asian patients
with newly diagnosed T2DM
RADHA CHITALE
Combined oral antidiabetic therapy with lin-
agliptin plus metformin was well tolerated
and successfully brought down HbA1c levels
in newly diagnosed Asian patients with type 2
diabetes mellitus (T2DM) with very high blood
sugar levels.
Linagliptin is a dipeptidyl peptidase (DPP)-4
inhibitor, a class of drug which has been shown
to lead to less weight gain and a lower risk of
hypoglycemia compared with insulin treatment.
A recent multinational trial of patients with
untreated T2DM for less than a year includ-
ed patients with HbA1c between 8.5-12 per-
cent who were randomized to linagliptin plus
metformin (n=159) or to linagliptin mono-
therapy (n=157). [Diabetes Obes Metab 2014.
doi:10.1111/dom.12399]
A subgroup of patients recruited from five
Asian countries (India, Sri Lanka, Malaysia, Phil-
ippines, Thailand) had baseline characteristics
among the linagliptin plus metformin (n=62)
and linagliptin monotherapy (n=63) groups
of median age about 48 years, median HbA1c
about 10 percent, and median fasting plasma
glucose of 188 mg/dL in the combination arm
and 195 mg/dL in the monotherapy arm. There
was some microvascular disease in both arms.
After 24 weeks, among the Asian patients,
mean reduction in HbA1c with combination ther-
apy was 3 percent compared with 1.84 percent
in the monotherapy group (p<0.0001).
Patients on combination therapy demonstrat-
ed early saturation of greater glycemic levels
such that by week 6 there was a significant differ-
ence in glucose levels between the study arms.
Patients with greater hyperglycemia (≥9.5
percent) experienced greater HbA1c reductions
by the end of the trial compared with those with
lower baseline HbA1c (<9.5 percent).
Sixty-percent of patients on combination thera-
py achieved HbA1c of <7 percent at week 24 com-
pared with 21 percent in the monotherapy arm. Pa-
tients on linagliptin alone gained about 1.3 kg while
those on combination therapy lost 0.45 kg.
There was a fairly low percentage of cases
of hypoglycemia, including severe hypogly-
cemia. There were some gastrointestinal dis-
orders reported, but none leading to discon-
tinuation in either arm.
“The combination of linagliptin plus metfor-
min led to clinically important HbA1c reduc-
tions... within a 24-week period,” said Dr. Ron-
ald Ma of the Chinese University of Hong Kong.
“This suggests that early combination [thera-
py] may be a useful strategy in Asian patients.”
He noted that the results represent a post-
hoc analysis of a small subgroup and that the
findings should benefit from the results of on-
going larger-scale trials.
5. JANUARY 2015 FORUM 5
Alcohol in all policies
Three years ago, I wrote an article for the Ma-
lay Mail mourning the loss of a friend and
colleague to an alcohol-induced heart attack. He
was 41 years old and left behind two teenagers
and a toddler. On his final night alive he had been
at one of our fundraising events, and even though
he was already drunk, slurring, stumbling, he
kept drinking. Too inebriated to drive home, he
fell asleep in his car that night and never again
woke up. It was bizarre to walk into the office the
weeks after and know that he was no longer there
– bizarre that I knew that simple public health reg-
ulations could have prevented his death. Public
health laws could have easily required that all al-
cohol servers not serve alcohol to persons who
are already drunk, or that free water be provided
at all venues where alcohol is served.
As a harm reductionist rather than a prohi-
bitionist, I was intrigued to receive an email in-
viting me to do a keynote speech at the IOGT
World Congress on Alcohol in All Policies in Cha
Am, Thailand, in late October 2014. IOGT, or the
International Organisation of Good Templars, is
a very old organization believing in temperance
and, in many cases, complete abstinence from
substances. A harm reductionist, on the other
hand, understands that despite prevention and
education programs, the wide availability of in-
toxicating substances (both licit and illicit) mean
Fifa Rahman
LLB (Hons), MHL (Health Law) (Sydney)
Policy Manager, European Union Asia Action and
Community Action on Harm Reduction (CAHR) Projects
“ Many harm reductionists think
it is great if someone can be
abstinent, but if they can’t, then
it is also great if they are stable
on medications, functioning
in society with a stable job,
and receiving counselling
and support they need ”
6. JANUARY 2015 FORUM 6
that there will always be drug use, and that mea-
sures must be taken to reduce harm to individ-
ual users, their families, and society as a whole,
without necessarily enforcing abstinence. While
I knew that there were ideological differences
between IOGT and myself in terms of some drug
and alcohol policies, the keynote request was in
relation to Alcohol Regulation and Trade Agree-
ments, on which we shared a common interest
and agreement. I agreed to give the speech and
travelled to Cha Am on 26 October 2014.
Day 1 of the academic program began with a
session on the upcoming United Nations Gen-
eral Assembly Special Session on Drugs in 2016
(hereinafter the UNGASS2016). The Special
Session is to be held following more-or-less a
worldwide consensus that the ‘War on Drugs’,
a senseless war rooted in fear-mongering, rac-
ism, and punitive rhetoric, has completely failed.
To quote Dr. Alex Wodak, former director of the
Drug and Alcohol Service at St Vincent’s Hos-
pital in Sydney, Australia, and president of the
Australian Drug Law Reform Foundation, it has
been “an expensive way of making a bad prob-
lem worse”. It concerned me greatly that IOGT
members considered harm reduction and hu-
man rights arguments to be a threat to IOGT
objectives. Harm reduction, of which needle-
and-syringe exchange, condom provision, and
methadone maintenance therapy is a part, has
been proven to successfully reduce HIV infec-
tion, increase referrals to drug treatment due to
increased interactions between drug users and
health workers, reduce overdose deaths, and
improve quality of life and general health. Many
harm reductionists think it is great if someone
can be abstinent, but if they can’t, then it is also
great if they are stable on medications, function-
ing in society with a stable job, and receiving
counselling and support they need. An anti-
harm reduction stance is one that is harmful to
public health.
Interestingly, in terms of alcohol use, there
was a clear difference in opinion among del-
egates about language used at the WHO in
terms of alcohol regulation. The main WHO
strategy for alcohol control and regulation is
titled the ‘Global Strategy to Reduce the Harm-
ful Use of Alcohol’. Pubudu Sumanasekara,
executive director of the Alcohol and Drug In-
formation Centre (ADIC) in Sri Lanka, stated
that the terminology ‘harmful use of alcohol’
as opposed to ‘use of alcohol’ was ‘one of the
successes of the alcohol industry’ in infiltrat-
ing public health policy. Øystein Bakke, senior
advisor of Forut Norway, an organization work-
ing in alcohol policy, drugs and development,
and women and children’s rights, disagreed,
and said: “the distinction may be losing a little
bit of its value,” and that enforcing the distinc-
tion could alienate people that you would want
to outreach to. Earlier, Bakke had pointed out
that contrary to the perception that alcohol de-
pendence and harmful use of alcohol was a
‘lifestyle disease’ particular to wealthy coun-
tries, the fact that 80 percent of non-communi-
cable disease deaths were in low- and middle-
income countries.
On the third day of the conference, I presented
on the impact of provisions in free trade agree-
ments on alcohol regulation. New generation
trade agreements, like the Trans-Pacific Partner-
7. JANUARY 2015 7
ship Agreement (TPPA) between the US and Ma-
laysia, Singapore, Vietnam, and Brunei, among
others, and the Transatlantic Trade and Invest-
ment Partnership (TTIP) between the US and Eu-
ropean Union, contain provisions that will restrict
the ability of states to make public health policy,
including alcohol regulations. The Wine and Spir-
its Annex of the TPPA, for example, would make
it difficult to place health warnings directly on the
labels of alcohol products. Governments may
have to settle for a supplementary label.
Martin-Moreno et al. in their 2013 article in
the European Journal of Public Health sug-
gested that what is needed is enhanced label-
ing with clear health warnings and nutritional
information printed on alcohol products. Such
a policy, under both the TPPA and TTIP, could
constitute a ‘technical barrier to trade’ and be
deemed an ‘expropriation of the value of in-
vestments’. In layman’s terms, enhanced label-
ing would reduce profits, and so the company
would be able to sue governments at interna-
tional tribunals. These tribunals have tradition-
ally been pro-investor, and award unlimited
damages based on expected profits of the
company.
Margaret Chan, executive-director of the
WHO, rightly said that these trade agreements
are being used to ‘handcuff governments’ when
acting to protect the health of its citizens. And
while technical, the basic premise is simple: that
trade agreements should not venture into public
health, and that civil society, academics, physi-
cians, and allied health professionals must rise
up against them.
“ In terms of alcohol use,
there was a clear difference
in opinion among delegates
about language used at the
WHO in terms of alcohol
regulation ”
8. JANUARY 2015 CONFERENCE COVERAGE 8
CHRISTINA LAU
Family physicians should be involved in the
provision of palliative care, particularly in the
patient-desired community setting, said experts.
“More than 90 percent of patients spend the
majority of their last year of life and receive pal-
liative care at home,” said Professor Rodger
Charlton of the Division of Primary Care, The
University of Nottingham, UK. “This places GPs
and family physicians at the heart of palliative
care provision. Indeed, they value this aspect of
their work greatly.”
“In Hong Kong, although ambulatory pallia-
tive care is available for the terminally ill, primary
care physicians have not been involved in the
provision of such care,” said Dr. Tin-Chak Hong,
Specialist in Family Medicine at the Hong Kong
Sanatorium Hospital. [HK Pract 2004;26:151-
155; Progress in Palliative Care 2011;19:109-
113; Tse MWD, Hospital Authority Convention
2012; HK Pract 2013;35:52-58]
Family physicians in Hong Kong are equipped
and ready to provide palliative care, Hong ar-
gued. “Through family medicine training, they
have acquired the concept and skills of a holistic
approach to care, especially in the psychosocial
aspect, which is the essence of palliative care,”
he said.
In fact, 96.8 percent of local family physi-
cians indicated in a survey that they should be
involved in the provision of palliative care, and
77.7 percent wished to provide palliative care in
their practice. [HK Pract 2013;35:36-51]
The survey, to which 48.1 percent of mem-
bers of the Hong Kong College of Family Physi-
cians responded, also showed that 58.2 percent
of family physicians were currently providing
some form of palliative care in their practice.
However, only 14 percent were providing home
visits.
“Barriers to family physicians’ provision of
community palliative care include cultural con-
Involve family physicians in community
palliative care, say experts
21st Hong Kong International Cancer Congress, The University of Hong Kong,
21 November 2014
9. JANUARY 2015 CONFERENCE COVERAGE 9
cerns, lack of time, lack of support and collabo-
ration networks with palliative care specialists
and the multidisciplinary team, and knowledge
gaps,” said Hong.
“Further enhancement of primary healthcare
systems, social and medical support, and ed-
ucation are needed to enable the provision of
continuity of care by teams involving family phy-
sicians,” he continued.
As for patients, 81.8 percent of those with
terminal cancer in a palliative care unit of a
public hospital in Hong Kong indicated they
wished to have home visits by healthcare pro-
fessionals when needed. Thirty-seven percent
wished to stay at home during the pre-termi-
nal period, while 19 percent wished to die at
home. [Hong TC, et al, Hospital Authority Con-
vention 2010]
“Two important elements of a ‘good death’
are to have choice and control over where death
occurs, and who is present and shares the end.
However, dying ‘naturally’ with dignity is be-
sieged by bureaucracy in both Hong Kong and
the UK,” said Charlton.
“As a result, inappropriate hospital admis-
sions are common in Hong Kong,” he contin-
ued. “Almost all elderly patients with terminal or
irreversible chronic illnesses die in an unfamiliar
acute hospital environment, where visiting time
is restricted and ward staff is unable to dedi-
cate time to offer a ‘good death’ experience to
patients or assist with bereavement.” [Asian J
Gerontol Geriatr 2011;6:103-106]
For GPs with an interest in providing pallia-
tive care, the question of whether they would be
surprised if a patient with advanced cancer died
in the following year was shown to provide an
accurate survival prognosis. According to re-
searchers, this ‘surprise’ question can be used
to help identify patients who may need end-of-
life care planning. [Palliat Med 2014;28:959-964]
“Having identified these patients, the next
step is to talk to them and their family members
about death, about their fears and concerns,”
said Charlton.
“There is a need for doctors to stop seeing
death as the enemy because death is not a fail-
ure of medicine; it is the inevitable result of life,” he
emphasized. “However, we sometimes try to keep
people alive longer than we should.”
“There is a growing movement of feeling that
we should be aiming for a good death and not
a prolonged one,” he continued. “We should
focus on building a healthcare system that will
help dying patients achieve what is important to
them. To a great extent, the quality of a health-
care system is reflected in the quality of end-of-
life care provision.”
“ Dying ‘naturally’ with dignity is
besieged by bureaucracy in both
Hong Kong and the UK ”
“ There is a need for doctors to stop
seeing death as the enemy because
death is not a failure of medicine”
10. JANUARY 2015 CONFERENCE COVERAGE 10
PANK JIT SIN
The findings of the Recognise Asthma and
Link to Symptoms and Experience (RE-
ALISE) survey reveals that asthma patients
can be segmented into distinct and action-
able groups based on their attitude towards
asthma.
Dr. Aileen David-Wang, clinical associate pro-
fessor, University of the Philippines – Philippine
General Hospital, said the survey was aimed at
“identifying distinct and explicit patient clusters
in Asia, defined by their differing attitudes, ad-
herence, educational needs and other important
attributes.”
The survey assigned patients into one of five
clusters – Well Adjusted; Rejector; Lost; Endur-
er; and Worrier. The attitudes of patients could
confidently determine their asthma control
based on the Global Initiative for Asthma (GINA)-
defined criteria. The Well Adjusted and Rejector
clusters typically had a high level of asthma con-
trol. The Lost and Endurer clusters experienced
low asthma control, while the Worriers had the
lowest control of asthma. Wang said each clus-
ter has different information needs and requires
a tailored management approach.
Through proper matching of patients’ atti-
tudinal cluster, doctors can optimally manage
asthma patients through personalized solutions
instead of a one-size-fits-all approach.
Wang went on to describe each cluster’s
character profile, with the Well Adjusted ones
being able to cope well with their asthma and
being minimally impacted in their daily lives,
both emotionally and functionally. Additionally,
they are happy to go along with their doctor’s
advice and have no problem using their inhaler
– a reflection of their carefree attitude and lower
stress levels.
The Rejectors are patients who have to come
to terms with the emotional burden of living with
asthma, and their asthma is generally well con-
trolled. The refusal to accept their disease state
is reflected in their tendency to deprioritize their
health. This cluster is also particularly conscious
about using the inhaler in public.
Those in the Lost cluster generally have a high
level of stress and anxiety about their poorly con-
trolled asthma. This leads to a rejection of their
asthma status, their doctor and their inhaler, said
Wang. The Lost tend to be evasive and avoid
thinking about their health problems (asthma),
despite being emotionally and functionally af-
fected by it. However, they frequently seek infor-
mation regarding asthma, suggesting that they
have unanswered questions and are at a loss for
answers.
Attitude determines outcome,
treatment strategy in asthma
19th Congress of Asian Pacific Society of Respirology (APSR), November
13-16, Bali, Indonesia
11. JANUARY 2015 CONFERENCE COVERAGE 11
Meanwhile, the Endurers are those who have
resigned themselves to the fact that they have
asthma and that they have no control over the
disease. Even though their level of confidence
in managing their asthma is low, the situation
doesn’t impact their daily life, emotionally or func-
tionally. The Endurers are fine with using their in-
haler (in public) and are less interested in finding
out more about asthma compared to other poorly
controlled clusters.
The cluster most troubled by their asthma
are the Worriers. To them, asthma is a constant
bother and always on their mind. Worriers are
able to come to terms with being labeled as
asthmatic and acknowledge the seriousness of
asthma, but live with a high level of stress and
anxiety over the disease. This is reflected in the
high level of concern they have regarding their
asthma and the high frequency of information
seeking, noted Wang.
12. JANUARY 2015 CONFERENCE COVERAGE 12
PANK JIT SIN
Man-made fibers are defined as those
whose chemical composition, structure
and properties are significantly modified during
the manufacturing process. These are spun and
woven into a number of consumer and industrial
products such as rayon, nylon and dacron. On
the other hand, natural fibers are composed of
biologically produced compounds such as cel-
lulose and protein. Such fibers emerge from the
manufacturing process in a relatively unaltered
state, for example, silk and cotton.
Speaking on the topic of man-made fibers and
the relationship with cancer, Professor Faisal Yu-
nus, senior lecturer, Department of Pulmonology
and Respiratory Medicine, Faculty of Medicine,
University of Indonesia, said the fibers studied were
made from various components and largely used
in the electrical and insulation industry, especially
wool and filament types.
The International Agency for Research on Can-
cer (IARC) has stated that there is inadequate evi-
dence of carcinogenic effects of glass wool, con-
tinuous glass filament rock wool, slag wool and
refractory ceramic fibers in humans. However,
experimental evidence abounds for carcinogenic-
ity of special-purpose glass fibers such as E-glass
and refractory ceramic fibers. [Available at http://
monographs.iarc.fr/ENG/Monographs/vol81/
mono81.pdf Accessed on 9 December]
Faisal noted that cancer is now a leading
cause of death, with 12.7 million new cases and
7.6 million deaths in 2008. The World Health
Organization (WHO) attributes 19 percent of all
cancers as being caused by the environment,
including at work, with about 1.3 million deaths
each year.
Of this number, one in 10 lung cancer deaths
are closely related to risks in the workplace. Ac-
cording to the WHO, lung cancer, mesothelioma
and bladder cancer are among the most com-
mon types of occupational cancers. For cancers
of the lung, arsenic, asbestos, coal, engine ex-
haust and chromium compounds are linked to
carcinogenicity in humans. Additionally, crystal-
line silica dust, soot, tobacco smoke and outdoor
particulates are also proven lung carcinogens.
However, there is insufficient evidence from
both animal and human studies for carcino-
genicity of fibers such as continuous glass
filament, alkaline earth silicate wool, high-
alumina, and low-silica wools. Data from ani-
mal studies indicating that man-made vitreous
fibers are potentially carcinogenic are also
inconclusive.
Harm from man-made fibers unclear
19th Congress of Asian Pacific Society of Respirology (APSR), November
13-16, Bali, Indonesia
13. JANUARY 2015 CONFERENCE COVERAGE 13
CHUAH SU PING
Air pollution is one of the major causes of
mortality globally.
“Ambient air pollution was estimated to have
caused an excess of 3.7 million premature
deaths in 2012, with 88 percent of these excess
deaths having occurred in low- and middle-in-
come countries,” said Professor Emeritus Nor-
bert Berend, head of Respiratory Research at
the George Institute for Global Health, Sydney,
Australia. He noted that the causes include rapid
industrialization, increased motor vehicle traffic
and the use of cheap coal as a source of power.
“The many effects of air pollution can be di-
vided into acute and chronic effects. Acute ef-
fects include respiratory symptoms, cardiovas-
cular events, hospitalizations and mortality, and
these are more pronounced in people with un-
derlying respiratory or cardiovascular diseases.
Chronic effects range from reduction of lung
growth in children and adolescents, reduced
lung function in adults and lung cancer,” said
Berend.
Berend highlighted the ‘Great Smog’ of 1952,
which was a severe air-pollution event that af-
fected London from December 5-8 in 1952. “The
Great Smog is known to be the worst air pollu-
tion to have ever occurred in the UK, and it is
Air pollution a leading preventable
cause of death worldwide
linked to at least 12,000 deaths. This event was
significant as it led to increased public aware-
ness, government regulation and environmental
research,” he said. “The level of pollution noted
in the 1952 smog in London, can now be seen
in key cities in China, in particular Beijing, and
India.”
“Indoor air pollution is also a major concern.
Up to 3 billion people rely on the burning of
biomass fuels indoors as a source of heating
or to cook, and this has been linked to approxi-
mately 4.3 million deaths yearly. Of that figure,
1.69 million deaths are from Southeast Asia,
and 1.62 million are from the Western Pacific
region,” said Berend. Worldwide, he noted, the
use of biomass fuels is especially high in ur-
ban slum populations.
“As healthcare practitioners, what we need
to do now is to continue to advocate for lung
health to the public, government health depart-
ments as well as international agencies. Whilst
it is important that we continue the anti-smok-
ing lobby, we must also demand an upgrading
of international air quality standards as well as
adherence to these standards. We also need
to push for increased research funding from
individuals, national and international respira-
tory societies to improve the field of respiratory
health.”
19th Congress of Asian Pacific Society of Respirology (APSR), November
13-16, Bali, Indonesia
14. JANUARY 2015 CONFERENCE COVERAGE 14
RADHA CHITALE
Natural disasters have significant direct and
indirect effects on lung health and can
have long-term repercussions, particularly in
the Asia-Pacific region, where 80 percent of the
world’s natural disasters in the 20th and 21st
centuries have occurred.
Earthquakes, tsunamis, volcano eruptions
and typhoons can be violent and dirty, exposing
people in the area to harmful particulate matter
and microbes. Efforts to gather people together
for care immediately after a disaster can lead to
further harm.
“Respiratory infectious diseases are the main
problem,” said Dr. Bruce Robinson of the Univer-
sity of Western Australia and director of the Na-
tional Centre for Asbestos Diseases Research in
Perth, Australia.
Following a tsunami, for example, there is wa-
ter everywhere creating lots of places for mosqui-
toes – the disease vectors – to breed.
Crowding following a disaster can lead to
rapid infection spread due to exposure. Diseases
such as measles, acute lower respiratory tract
infection, and tuberculosis – all of which can be
fatal without prompt, appropriate treatment – can
spread quickly.
Following the 2004 earthquake and tsunami
that hit parts of Thailand, more than half (62 per-
cent) of the consultations for communicable dis-
Natural disasters can affect lung health
eases, about 180,000, occurred within the first 12
weeks following the disaster.
Large natural disasters can cause existing
healthcare services to break down resulting in a
lack of medical care for routine pulmonary events.
Healthcare workers are also at risk for physical
injury, infection, and may be worried about the
safety of their own families.
Patients with existing pulmonary disease are
at risk during natural disasters if there are disrup-
tions to power for oxygen delivery, routine medi-
cines for asthma or chronic obstructive pulmo-
nary disorder, or if there is no physiotherapy or
other services for people with chronic diseases
like cystic fibrosis.
To be prepared, Robinson recommended
backup power sources, medication stores,
and adequate transport plans to move patients
to better facilities. [Respirology 2011;16:386-
395]
There are four main direct effects of disasters
on the lungs.
Small particles of smoke or toxic gases from
fires or volcanic emissions can be inhaled, and
if they are hot the lungs can burn, become leaky,
and be poisoned by carbon monoxide.
The 1997 haze fires in Indonesia caused over
500 haze-related deaths in 3 months as well as
300,000 cases of asthma, 50,000 cases of bron-
chitis, and 1.5 million respiratory infections, Rob-
inson said.
19th Congress of Asian Pacific Society of Respirology (APSR), November
13-16, Bali, Indonesia
15. JANUARY 2015 CONFERENCE COVERAGE 15
Aspirating water can introduce water-borne
pathogens to the lungs. Direct trauma to the chest
when buildings fall down can result in rib fractures
or diaphragm rupture.
Psychological trauma following a natural di-
saster can also result in physical manifestations
that need to be managed, Robinson said.
“As a chest physician, it’s important to engage
with the psychological trauma after a disaster...
What I’ve found is that it’s very important to talk
to the patients because no one else is talking to
them,” he said. Particularly when a mass group is
affected, it becomes important for the doctor to
engage.
16. JANUARY 2015 CONFERENCE COVERAGE 16
Fracture risk in diabetics
underestimated
IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting 2014, November
14-16, Taipei, Taiwan – Chuah Su Ping reports
The potential for fracture in patients with dia-
betes may be underestimated, as some of
the major fracture assessment tools that are
available do not take into account diabetes as
a risk factor.
“Fractures are a common complication of
diabetes, with common fracture sites including
the hip, wrist and spine,” said Dr. Jung Fu Chen
of the Division of Endocrinology and Metabo-
lism (Osteoporosis Clinic) at Chang Gung Me-
morial Hospital, Kaohsiung, Taipei. “However,
despite the metabolic abnormalities of diabe-
tes which do affect bone metabolism, structure
and bone mineral density (BMD), the associa-
tion between increased fracture risk in individu-
als with type 1 and 2 diabetes continues to be
debated.”
Chen noted that the current algorithm of the
WHO fracture risk assessment tool (FRAX®
)
does not include diabetes as a risk factor. In
2012, researchers reported that diabetes was
a significant predictor of subsequent major
osteoporotic fracture after controlling for age,
sex, medication use and FRAX risk factors in-
cluding BMD. Diabetes, they reported, was
also associated with significantly higher risk
for hip fractures (p0.001). [J Bone Miner Res
2012;27:301-308]
The investigators concluded that the FRAX
underestimated observed major osteoporot-
ic and hip fracture risk in diabetics (adjusted
for competing mortality), thus suggesting that
diabetes might be considered for inclusion in
future iterations of FRAX. “However, more re-
search is required in collecting new population
cohorts worldwide before this risk factor can be
included in the FRAX,” Chen opined.
More recently, a Taiwanese study evaluat-
ed fracture risk and post-fracture mortality in
patients with diabetes. Using data obtained
from Taiwan’s National Health Insurance Da-
tabase, they identified 32,471 adults with
newly diagnosed diabetes from 2000-2003;
and fracture events from 2000-2008 from
medical claims.
Based on 652,530 person-years of follow-
up, they noted that the incidences of fracture
for people with and without diabetes were 24.2
and 17.1 per 1,000 person-years, respectively
17. JANUARY 2015 CONFERENCE COVERAGE 17
(p0.0001). Compared with people without
diabetes, diabetics face a higher risk of frac-
ture (HR, 1.66, 95% CI, 1.60-1.72). “The study
also found that the odds ratios of post-fracture
deep wound infection, septicemia, and mortal-
ity associated with diabetes were 1.34 (95% CI,
1.06-1.71), 1.42 (95% CI, 1.23-1.64) and 1.27
(95% CI, 1.02-1.60), respectively,” said Chen.
[Diabetes Care 2014;37:2246-2252]
Similarly, investigators from the Atheroscle-
rosis Risk in Communities (ARIC) Study – a
US-based study with patients recruited from
four US communities – had reported that di-
agnosed diabetes was significantly and inde-
pendently associated with an increased risk of
fracture. The ARIC study supports recommen-
dations from the American Diabetes Associa-
tion for assessment of fracture risk and imple-
mentation of prevention strategies in persons
with diabetes, particularly those with poor glu-
cose control. [Diabetes Care 2013;36:1153-
1158]
“With the ever-growing population of diabet-
ics in Asia, coupled with an increasing aging
population, a multidisciplinary team approach
which includes bone care is very crucial for the
integrated management of diabetic patients,”
concluded Chen.
18. JANUARY 2015 CONFERENCE COVERAGE 18
Osteoporotic fractures in men –
highlights from the MrOS study
IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting 2014, November
14-16, Taipei, Taiwan – Chuah Su Ping reports
Fractures resulting from osteoporosis are a
major healthcare challenge in men, yet the
rate of detection and management of male os-
teoporosis lags well behind that in women, ac-
cording to an expert.
The residual lifetime risk of experiencing an
osteoporotic fracture in men 50 years old and
above is estimated to be approximately 27 per-
cent. [Osteoporosis Int 2001;12:124-130] In
comparison, the risk of developing prostate can-
cer in men over the age of 50 has been calcu-
lated at around 11 percent. [Cancer Epidemiol
Biomarkers Prev 1997;6:763-768]
“The Osteoporotic Fractures in Men (MrOS)
Study is a prospective cohort study designed
to examine the extent to which fracture risk
is related to bone mass, bone geometry, life-
style, anthropometric and neuromuscular
measures, and fall propensity, as well as to
determine how fractures affect quality of life
in men,” said Dr. Eric Orwoll, professor of
Medicine and director of the Bone and Mineral
Clinic at Oregon Health and Science Universi-
ty, Portland, Oregon, US. [Contemp Clin Trials
2005;26:569-585]
“To date, the MrOS study has helped estab-
lish that although women have a higher risk of
fracture, the association between bone mineral
density (BMD) and fracture risk is clearly evi-
dent in men, and similar to that in women,” said
Orwoll. [J Bone Miner Res 2006;21:1550-1556]
More recently, another paper from the MrOS
study noted that men with accelerated femoral
neck BMD loss had an increased risk of hip and
other non-spine fractures. [J Bone Miner Res
2012;27:2179-2188]
“While the MrOS study has provided fur-
ther understanding of osteoporosis fractures in
men, it did also raise questions. [One] study,
for example, raised the question of whether or
not men with low-to-normal BMD (not yet in the
range requiring treatment) should have a repeat
[BMD] measurement in 2-to-3 years, and wheth-
er or not to treat men with the greatest rate of
19. JANUARY 2015 CONFERENCE COVERAGE 19
bone loss earlier,” said Orwoll. The researchers
concluded that further research was still need-
ed in order to determine if repeat BMD testing
and subsequent treatment in such a popula-
tion would be cost effective. [J Bone Miner Res
2012;27:2179-2188]
Orwoll also highlighted a MrOS substudy
which showed an association between poor
physical performance and the likelihood of in-
cident vertebral fractures. “The investigators
concluded that men who performed poorly on
several tests – chair stand, walking speed, leg
power, narrow walk and grip strength – had
twice the risk of radiographic vertebral frac-
tures over time compared with men who did
not perform poorly on any test,” said Orwoll. [J
Bone Miner Res 2014;29:2101-2108]
“The MrOS study is still ongoing, and next
phase aims to provide further understanding
of the trajectories of change in musculoskel-
etal health, and how they affect important
outcomes such as fracture, and physical dis-
ability,” said Orwoll. “Using high resolution mi-
cro-computed tomographic imaging, our goal
is to further assess the relationship between
bone microstructure and fracture risk.”
20. JANUARY 2015 CONFERENCE COVERAGE 20
Soy food intake is associated with a reduced
risk of osteoporotic hip fractures in women
but not in men, according to research from the
Duke-NUS Graduate Medical School, Singa-
pore. 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.
“The incidence of hip fractures is rising in
Asia, in part due to the rapidly aging popula-
tion, however there is still a paucity of studies
among Asian populations on the dietary factors
of osteoporosis,” said Duke-NUS researcher
Associate Professor Koh Woon Puay. Koh and
her team prospectively examined the associa-
tions of dietary intakes of soy isoflavones and
carotenoids with hip fracture risk among elderly
Chinese in the Singapore Chinese Health Study,
a prospective cohort of 63,257 men and women
45-74 years of age.
In their paper, Koh and colleagues noted that
soy food products, such as plain tofu, taupok,
taukwa, foopei, foojook, tofu-far and soybean-
drink, are common in the Singapore Chinese diet.
“Total soy isoflavone intake for a given sub-
ject was computed based on the food frequency
questionnaire (which all participants were re-
quired to complete) and the summation of the
[isoflavone] content of all the seven soy foods
in the Singapore Food Composition Database,”
she said.
“This is the first study to compare the effects
of soy on hip fracture between men and wom-
en in a cohort study,” noted Koh. “Our study
revealed a significant reduction in hip fracture
in women with moderate intakes of soy isofla-
vones. Conversely, no protective association
was found in men with similar intakes.” [Am J
Epidemiol 2009;170:901-909]
Koh noted that this is consistent with previ-
ous animal studies which showed that expo-
sure to the isoflavone genistein was linked to
increased bone marrow density in the femurs of
adult female mice but not in male mice. [Pediatr
Res 2007;61:48-53]
With regards to carotenoid intake and hip frac-
ture risk, Koh noted that among men, consump-
tion of vegetables – the main source of carotenoid
intake in this population – was associated with
lower hip fracture risk. Similarly, dietary intake
of total carotenoids and specific carotenoids –
α-carotene, β-carotene, and lutein/zeaxanthin –
were inversely associated with hip fracture risk.
Soy isoflavones and carotenoids
have gender-specific protective
roles against hip fractures
IOF Regionals, 5th Asia-Pacific Osteoporosis Meeting 2014, November
14-16, Taipei, Taiwan – Chuah Su Ping reports
21. JANUARY 2015 CONFERENCE COVERAGE 21
“When stratified by body mass index (BMI),
the greatest protective effects of total vegetables
and carotenoids were found in lean men (BMI
20 kg/m2
),” said Koh. “There was no associa-
tion between dietary carotenoids or vegetables/
fruits, and hip fracture risk among women.” The
authors postulated that the antioxidant effects of
carotenoids may counteract the mechanism of
osteoporosis related to leanness. [J Bone Miner
Res 2014;29:408-417]
Koh concluded that, based on the hypothe-
ses attained from these two studies, future inter-
ventional studies should target different mecha-
nisms in osteoporotic fractures.
High resolution micro-computed tomograph-
ic imaging, our goal is to further assess the rela-
tionship between bone microstructure and frac-
ture risk.”
Odanacatib promising therapy
for osteoporosis in men
Odanacatib, a selective inhibitor of cathep-
sin 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
2014;25:571(OC1)]
“In a phase II study in postmenopausal wom-
en, treatment with odanacatib 50 mg once week-
ly resulted in increases in bone mineral density
(BMD) at the lumbar spine (11.9 percent) and
total hip (8.5 percent) over 5 years,” said Profes-
sor Eric Orwoll, director of the Bone and Mineral
Clinic, and of the Bone Density Lab at Oregon
Health and Science University, Portland, US. [J
Bone Miner Res 2012;27:2251-2258]
“Men with osteoporosis represent between
20 and 25 percent of all osteoporotic patients
and men are at greater risk of death following a
hip fracture. Following the promising results of
the phase II study in postmenopausal women,
we carried out a double-blind, placebo-con-
trolled 24-month study to evaluate the safety
and efficacy of odanacatib for the treatment
of men with osteoporosis,” said Orwoll. “This
is the first study of odanacatib in men with
osteoporosis.”
The primary objectives of their study were to
assess the effect of odanacatib 50 mg weekly
versus placebo on lumbar spine BMD over 24
months; and to assess the safety and tolerability
22. JANUARY 2015 CONFERENCE COVERAGE 22
of odanacatib 50 mg weekly compared with pla-
cebo. “We enrolled men 40-95 years of age with
idiopathic osteoporosis or osteoporosis associ-
ated with hypogonadism (total serum testoster-
one ≤250 ng/dL). Participants were randomized
to either the study drug or placebo once weekly,
and all received vitamin D3 (5,600 IU/week) and
calcium supplements (total intake approximate-
ly 1,200 mg daily),” noted Orwoll.
Compared with placebo, treatment with odan-
acatib 50 mg weekly for 24 months increased
lumbar spine, total hip, femoral neck and trochan-
teric BMD. “We noted decreased levels of mark-
ers of bone resorption in the odanacatib group
versus placebo. While markers of bone forma-
tion initially decreased [in the odanacatib group],
these were then noted to return toward levels
similar to that observed in the placebo group by
month 24,” said Orwoll. The investigators noted
that the adverse events and overall safety profile
were similar between both study groups.
“These data indicate that odanacatib therapy
is effective in increasing spine and hip BMD in
men with osteoporosis. Changes in bone turn-
over markers suggest that odanacatib treatment
decreases bone resorption while producing rela-
tively small decreases in bone formation. Thus,
this cathepsin K inhibitor may be a promising po-
tential therapy for the treatment of osteoporosis
in men,” Orwoll concluded.
23. JANUARY 2015 CONFERENCE COVERAGE 23
Acute 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 mor-
bidity and mortality,” said Associate Profes-
sor Ida Hilmi, a consultant in gastroenter-
ology, University of Malaya, Kuala Lumpur,
Malaysia. “The clinical course of the dis-
ease typically manifests with remissions
and exacerbations characterized by rectal
bleeding and diarrhea. Medical therapy can
only ameliorate the inflammatory process
and control most symptomatic flares but
provides no definitive treatment for the dis-
ease.”
Acute severe ulcerative colitis is usually
defined according to the original criteria
set forth by Truelove and Witts – frequent
loose bloody stools (≥6 per day) with evi-
dence of systemic toxicity as demonstrated
by fever (≥37.8°C), tachycardia (heart rate
[HR] 90 bpm), anemia (Hb 10.5 g/dL) or
an elevated erythrocyte sedimentation rate
(HR) 30 mm/h.
“Clinicians should be able to rule out
precipitating or other causes and assess
the need for emergent surgery,” Hilmi said.
Stool microscopy and culture should be
performed as part of the initial assessment,
as well as a test for Clostridium difficile in-
fection. “This is because pseudomembra-
nous colitis can complicate or mimic severe
ulcerative colitis. Plain abdominal radio-
graphs are also important to look for toxic
megacolon or to rule out perforation.”
For patients who meet the clinical criteria
for severe ulcerative colitis, sigmoidoscopy
and a biopsy may be required to look for
cytomegalovirus (CMV), the presence of
which may result in treatment failure. En-
doscopic scoring system (eg, the modified
Baron score) may be used to assess for dis-
ease severity. Some patients, however, may
have severe ulcerative colitis at endoscopy,
despite not fulfilling the clinical criteria for
severity, said Hilmi.
Intravenous corticosteroids (hydrocor-
tisone 100 mg four times daily or meth-
Challenges in the management
of acute severe ulcerative colitis
Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia –
Elvira Manzano reports
24. JANUARY 2015 CONFERENCE COVERAGE 24
ylprednisolone 60 mg daily) remain the
mainstay of treatment for severe ulcerative
colitis. Careful monitoring of stool frequen-
cy and vital symptoms, as well as abdomi-
nal examination, is necessary to assess the
patient’s response to therapy. The use of
antibiotics may be justified in those with co-
existing sepsis, she added.
For patients with steroid-refractory coli-
tis, rescue therapy with cyclosporine or inf-
liximab must be commenced. In one study,
intravenous infliximab was no more effec-
tive than intravenous cyclosporine in pa-
tients with acute severe ulcerative colitis
refractory to intravenous steroids. [Lancet
2012;380:1909-195]
“Well-timed rescue medical therapy is
generally safe when administered by ex-
perienced physicians, and is effective in
the majority of cases,” said Hilmi. “Close
liaison with the surgeon is essential as the
window for timely surgery is narrow and de-
layed surgery, when it is required, can lead
to significant complications.”
25. JANUARY 2015 CONFERENCE COVERAGE 25
There is a need for simple tests to assist the
accurate diagnosis and prognostic assessment
of patients with inflammatory bowel disease
(IBD), says an expert.
“Serological antibodies are helpful in this
setting, but with major limitations,” said Pro-
fessor Michael A. Kamm from St. Vincent’s
Hospital and the University of Melbourne in
Melbourne, Australia. “Most of the described
antibodies found in IBD are autoantibodies di-
rected against enteric microbial epitopes and
are thought to arise secondary to the disease
process but are not thought to play a patho-
genic role.”
Perinuclear antineutrophil cytoplasmic an-
tibodies (pANCA) and anti-Saccharomyces
cerevisiae antibodies [ASCA], for example,
may have diagnostic value and are helpful in
distinguishing Crohn’s disease (CD) from ul-
cerative colitis (UC) and intestinal tuberculo-
sis (TB). However, they have limited prognos-
tic value,” said Kamm. “There is the presence
of a large number of detectable antibodies
[in the serum] that are associated with worse
long-term prognosis.”
Clinicians should also keep in mind that
antibody incidence in IBD is affected by spe-
cific disease, geography and ethnicity. Hence,
serologic responses differ between Asian and
Western populations. [World J Gastroenterol
2013;19:6207-6213]
Of note, none of the currently available se-
rological markers for IBD can be used as a
stand-alone diagnostic in clinical practice and
can only serve as an adjunct to endoscopy,
which is quite invasive.
As clinical aid, C-reactive protein (CRP) has
been the typical laboratory marker used for
differentiating IBD from functional and other
bowel disorders. CRP is an objective marker
of inflammation and correlates well with dis-
ease activity in CD. However, it is still far from
ideal, said Kamm.
“It is nonspecific ... measures inflammation
but it does not tell us where the inflammation is
occurring. There is also remarkable heterogene-
ity in the CRP response between CD and UC.”
Serologic and fecal biomarkers in
IBD: Can they replace endoscopy?
Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia –
Elvira Manzano reports
26. JANUARY 2015 CONFERENCE COVERAGE 26
Recently, several fecal biomarkers have
been developed that are sensitive indicators
of active intestinal inflammation and may pro-
vide a convenient method to assist in the di-
agnosis and prognosis of patients with IBD.
“The best proven biomarker is calprotectin, a
neutrophil-derived protein which is stable in
feces and can be quantitatively measured in
stool. It is useful in distinguishing IBD from
functional symptoms and in monitoring dis-
ease recurrence. Fecal testing of calprotectin
can also in some circumstances replace en-
doscopy.”
Fecal calprotectin is easy to measure, and
is reproducible. The test is also inexpensive.
“Fecal calprotectin is likely to play an increas-
ingly important role in the management of
IBD, Kamm said.
27. JANUARY 2015 CONFERENCE COVERAGE 27
Improving CRC risk stratification
through simple criteria scores
Risk stratification in colorectal cancer (CRC)
patients with the Asia-Pacific CRC Screening
(APCS) score can help reduce the risk of morbid-
ity 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 manpow-
er, and improve public awareness via self-assess-
ment of CRC risk,” said Clinical Associate Profes-
sor Han-Mo Chiu of the National Taiwan University
and Hospital and the Asia-Pacific Working Group
on Colorectal Cancer.
The APCS score is a simple set of criteria that
classifies patients into average, moderate and high
CRC risk based on age, gender, family history of
CRC and smoking status. [Gut 2011;60:1236-1241]
The Asia Pacific region has a low rate of screen-
ing, ranging from about 33 to 40 percent across
Taiwan, Japan, Korea and, at the high end, Austra-
lia. Low public awareness is part of the problem,
but physicians play a key role in recommending
screening.
Current international guidelines recommend
screenings about every 10 years if a colonoscopy
is normal or if there are small adenomas, and ev-
ery 3 years if there are more than three adenomas
or one advanced neoplasm.
Lifestyle factors, particularly smoking and
weight, are significant contributors to higher CRC
risk. Metabolic syndrome increases the risk of
proximal and synchronous neoplasms, Chiu said,
as well as advanced neoplasm occurrence.
Increasing physical activity, reducing waist
circumference, smoking and alcohol intake, and
improving diet can reduce the risk of CRC by 23
percent. [BMJ 2010;341:c5504]
Coupling primary prevention via lifestyle chang-
es with increased early screening has the potential
to reduce the risk of CRC in at-risk patients, par-
ticularly in the Asia Pacific region. US data from
1975 to 2006 has shown that screening and early
treatment contributed to half of the CRC incidence
reduction (26 percent) during that period. Re-
duced mortality was attributed in significant part to
risk factor modification (35 percent) and screening
(53 percent) and only partially to advances in CRC
treatment (12 percent). [Cancer 2010;116:544-
573]
Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia –
Radha Chitale reports
28. JANUARY 2015 CONFERENCE COVERAGE 28
Early surgery may benefit Crohn’s
disease patients
The incidence of Crohn’s disease is increasing
in Asia and besides medical treatment and di-
etary changes, earlier surgery may be an appropri-
ate treatment option, research shows.
Crohn’s disease, a type of inflammatory bowel
disease that can affect the entire gastrointestinal
tract, is on a steady upward trend in countries in-
cluding Hong Kong, Korea, and Japan, according
to Dr. Kentaro Sugano of Jichi Medical University in
Shimotsuke, Tochigi, Japan.
In general, international guidelines suggest be-
ginning with anti-inflammatory medications and in-
corporating digestible nutrients into an “elemental
diet” composed of easily digestible liquid amino
acids, fats, sugars, minerals and vitamins, in pa-
tients with mild to moderate Crohn’s disease.
This may be followed by more medications (an-
tibiotics, immunosuppressants, corticosteroids),
nutritional therapy, and granulocyte aphoresis.
Surgery, in addition to medication and nutritional
therapy, is recommended for severe Crohn’s dis-
ease. [MHLW Research Group Report 2013]
For people whose Crohn’s disease is localized
in the distal ileum, surgery may be an appropri-
ate early intervention, Sugano said, with beneficial
long-term recurrence rates.
In one study of 55 patients with Crohn’s disease
who underwent resection surgery, over a median
6.7 years of follow up, 32 patients remained relapse-
free. Five patients required resection for recurrent
disease but body image and comesis scores im-
proved overall. [Br J Surg 2010;97:563-568]
“Taking into account the benefits and risks of
medical treatment and surgery, the risk of recur-
rence after surgery, individual preferences and any
personal or cultural considerations... surgery can
be less expensive and may have a better long-term
outcome,” Sugano said.
Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia –
Radha Chitale reports
29. JANUARY 2015 CONFERENCE COVERAGE 29
When should physicians stop HBV
therapy?
Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia
RADHA CHITALE
Anew 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 im-
proving patient outcomes, said Dr. Muhammad
Umar of the Centre for Liver and Digestive Dis-
eases at the Holy Family Hospital in Rawalpindi,
Pakistan.
Globally, about 2 billion people have or
have had an HBV infection. Up to 40 percent
develop liver failure or hepatocellular carci-
noma (HCC) and about 1 million people die
each year from HBV-associated liver disease.
[WHO Fact Sheets, www.who.int; N Engl J Med
1997;337:1733-1745]
HBV patients can be categorized into three
groups: complete viral response (viral load 60
IU/mL), partial or response (viral load 60 to
2,000 IU/mL), and inadequate response (viral
load ≥2,000 IU/mL). These are determined after
patients are assessed for primary non-response
after starting treatment at week 12 and again for
early predictors of efficacy via viral load at week
24. [Keeffe EB et al. Clin Gastroenterol Hepatol.
In press.]
Based on the viral response, patients may
have no change in treatment and broadened
monitoring, no change in treatment and close
monitoring, or they may need to switch to or add
an alternative therapy and receive extremely
close monitoring if they have inadequate viral
response.
However, seroconversion, which is wide-
ly accepted as the primary endpoint for HBV
treatment, is not useful for certain types of
less responsive HBV patients – those who
are HBV e antigen (HbeAg)-negative mu-
tants in the precore and core promoter re-
gions.
For these patients relapse is common af-
ter stopping oral therapy.
“Therapy is usually administered long-
term,” Umar said. “But several years of un-
detectable HBV DNA may decrease the re-
lapse rate.”
By comparison, in HBeAg-positive pa-
tients, who are the wild type, seroconver-
sion can be used to measure whether the
HBV viral load has reduced and, when it be-
comes low or undetectable, therapy may be
discontinued 6-12 months after seroconver-
sion. However, Umar said the durability of
response would be about 80 percent.
30. JANUARY 2015 CONFERENCE COVERAGE 30
Novel therapeutic interventions
for gastroparesis
Asian Pacific Digestive Week 2014, November 22-25, Bali, Indonesia
ELVIRA MANZANO
The 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 Pro-
fessor Gerald Holtmann from the Department
of Gastroenterology and Hepatology, Prin-
cess Alexandra Hospital and the University of
Queensland in Brisbane, Australia. “Gastropa-
resis is also thought to play an important role
in the manifestation of symptoms in patients
with functional dyspepsia. Thus, normalization
of gastric emptying may be targeted to relieve
symptoms in patients with functional dyspep-
sia or to control glucose in those with diabetic
gastroparesis.”
Apart from diabetes, common causes are
idiopathic and post-surgical as a consequence
of vagal nerve injury following upper abdominal
surgery, resulting in reduced pyloric relaxation
and impaired antral contraction.
Pharmacologic management include medi-
cations targeting dopaminergic or serotoniner-
gic pathways such as metoclopramide, dom-
peridone, cisapride, prucalopride, or itopride.
Inhibiting acetylcholinesterase activity to im-
prove gastric motility and emptying is also an-
other therapeutic approach, said Holtmann.
“Erythromycin derivatives devoid of antibiotic
properties are also considered promising candi-
dates for the treatment of gastroparesis. Eryth-
romycin given at low doses stimulates gastro-
intestinal motility and substantially accelerates
gastric emptying,” he added.
Interestingly, normalization or improvement
of gastric emptying in response to prokinetics is
not linked to improvement in symptoms. In one
study, for example, treatment with ABT-229, an
erythromycin derivative, was no more effective
than placebo in relieving symptoms in patients
with or without delayed gastric emptying. Upper
abdominal discomfort severity scores were simi-
lar between the two groups at 4 weeks. [Aliment
Pharmacol Ther 2000;14:1653-1661]
31. JANUARY 2015 CONFERENCE COVERAGE 31
For patients with refractory gastroparesis,
gastric electrical stimulation has been shown to
reduce symptoms, particularly nausea and vom-
iting, in small open-label studies. More recently,
intrapyloric injection of botulinum toxin has been
successfully trialled in small group of patients.
“While traditionally more invasive surgical in-
terventions [pyloro-myotomies, gastro-jejunos-
tomies] have been used to treat gastroparesis,
transpyloric stents have been trialled in selected
cases. Symptom control appears successful,
but there is questionable effect with regard to
other outcome parameters,” said Holtmann.
For refractory patients who have failed other
measures, a gastrectomy may be the only op-
tion.
32. JANUARY 2015 DRUG PROFILE 32
MAS064D: A new non-steroidal
topical treatment for mild-to-
moderate seborrheic dermatitis
Seborrheic dermatitis is a condition that affects approximately 1-3 percent of healthy
adults, occurring more frequently in men than women. A number of mainstream
medications typically used for seborrheic dermatitis include antifungals, topical
corticosteroids and keratolytics. Antihistamines may also be used to relieve itching.
MAS064D (SEBCLAIR®
Cream, Sinclair Pharmaceuticals) is a topical seborrheic
dermatitis treatment approved in the European Union (EU) and the United States.
Ee Lyn Tan, PhD
Seborrheic dermatitis
Seborrheic dermatitis (SD) is a common,
chronic and recurrent inflammatory derma-
tological condition typically characterized by
erythema, scaling and itchiness. [Clin Derma-
tol 2013;31:343-351] Typically, SD involves the
areas with a high density of sebaceous glands.
The scalp, face, upper chest, shoulders, flexures
and pubis are often involved. [J Eur Acad Der-
matol Venereol 2008;22:290-296] In infants, SD
typically occurs on the scalp (referred to as cra-
dle cap) causing a thick, yellowish ‘crust’ along
the hairline. Infant SD is usually self-limiting and
treatments are seldom required. However, SD in
adults can last from weeks to years and topical
treatments are often required.
SD is more common and more severe in im-
munocompromised patients, particularly patients
infected with the human immunodeficiency virus
(HIV). [N Engl J Med 2009;360:387-396] Lipo-
philic yeasts of the Malassezia genus, as well as
genetic, environmental and general health factors
contribute to this disorder. [Am Fam Physician
2000;61:2703-2710, 2713-2714]
Although SD is frequently seen in clinical
practice, much controversy remains regarding
its pathogenesis. Much of this controversy may
be related to its classification in a spectrum of
cutaneous conditions from dermatitis, fungal
Table 1: Constituents of MAS064D cream and their mechanisms of action
Ingredients
Concentra-
tion (%)
Activity
Active ingredients
Isohexadecane 8 Emollient
Shea butter 6 Emollient
Bisabolol 1.2 Anti-inflammatory
Piroctone olamine 1 Antimycotic
Alglycera 1 Anti-inflammatory keratolytic
Vitamin E 1 Anti-inflammatory antioxidant
Allatoin 0.35 Keratolytic
V. vinifera 0.1 Antioxidant
Telmesteine 0.01 Anti-inflammatory antioxidant
Vehicle
Aqua Moisturizer
Ethylhexylpalmitate Emollient
Isohexadecane Emollient
Cera alba Emollient
Butylene glycol Moisturizer
Propyl gallate Antioxidant
Adapted from J Eur Acad Dermatol Venereol 2008;22:290-296
33. JANUARY 2015 DRUG PROFILE 33
infection and inflammatory disease. [Clin Der-
matol 2013;31:343-351] For this reason, a va-
riety of treatments from topical corticosteroids
to topical antifungals and antimicrobials have
been used.
Treatment and management
SD is characterized by the cycle of remission
and flare. Treatment and management strate-
gies aim to relieve acute symptoms and provide
long-term prophylaxis to decrease the frequen-
cy and severity of recurrences. [Clin Dermatol
2009;27:S48-53]
Regular skin cleansing to remove oils from
sebaceous areas can improve the symptoms
of SD. Outdoor recreation will also improve
seborrhea, although sunscreen should be
used to avoid sun damage. [Am Fam Physician
2000;61:2703-2710, 2713-2704]
Pharmacological treatments for SD include
antifungal preparations that decrease coloniza-
tion with Malassezia spp. yeast (eg, selenium
sulfide, azole agents, topical terbinafine) and
anti-inflammatory agents (eg, topical cortico-
steroids). For severe SD, keratolytics such as
salicylic acid or coal tar preparations may be
used in conjunction with topical corticosteroids.
Scales can be removed by applying any of a va-
riety of oils (eg, peanut, olive or mineral). Over-
night application softens the scale and coal tar
shampoo may be used subsequently.
In patients with refractory disease, sebosup-
pressive agents such as isotretinoin may be
used as a last resort to reduce sebaceous gland
activity. [Am Fam Physician 2000;61:2703-2710,
2713-2704]
MAS064D (Sebclair®
Cream)
Indicated for the management of itching,
burning, scaling and pain associated with SD,
MAS064D cream is a steroid- and immunomod-
ulator-free topical treatment containing multiple
active ingredients (Table 1). [J Eur Acad Derma-
tol Venereol 2008;22:290-296]
Efficacy
MAS064D demonstrated good antifungal ac-
tivity in animal studies. Using guinea pigs infect-
ed with Malassezia furfur, MAS064D was tested
against ciclopirox olamine 0.77 percent cream
and a control group (no treatment). Erythema
and edema were not visually observed in any
of the infected animals at the end of the study.
In the animals treated with MAS064D and ci-
clopirox, Malassezia furfur counts were reduced
to below the limit of quantitation. [Clin Dermatol
2009;27:S41-43]
A multinational pilot study was conducted to
evaluate the efficacy and safety of MAS064D in
the treatment of mild-to-moderate facial SD. In
this randomized, double-blind, controlled study,
60 patients with SD were randomized to receive
either MAS064D (n=40) or a matching vehicle
(control; n=20). After 4 weeks, results showed
a higher percentage of treatment success (ac-
cording to investigators’ global assessment) in
the MAS064D than the control group (68 versus
11 percent, p0.0001). The effects of MAS064D
were also significantly better than those of the
control vehicle for investigator-assessed erythe-
ma and scaling, and patient-assessed pruritus
and global response to MAS064D (p≤0.01). [J
Eur Acad Dermatol Venereol 2008;22:290-296]
34. JANUARY 2015 DRUG PROFILE 34
An open label, single-center, bilateral pi-
lot study assessed the antifungal activity of
MAS064D cream against Malassezia spp, which
is commonly associated with SD. Only 10 healthy
volunteers were involved in this pilot study. The
study found that MAS064D reduced the number
of Malassezia spp colony-forming units (94 ver-
sus 49 percent on treated and untreated areas,
respectively; p=0.03). This pilot study shows the
nonsteroidal topical cream has antifungal activi-
ties. [Clin Dermatol 2009;27:S44-47]
In another investigator-blinded, randomized,
parallel-group, multicentre pilot study conducted
to compare the safety and efficacy of MAS064D
and desonide 0.05 percent cream for the treat-
ment of mild-to-moderate SD of the face, 77
patients were randomized to receive either
MAS064D or desonide cream for up to 28 days.
This study showed that both treatments were
as effective in reducing disease severity, with
approximately 90 percent of participants clear-
ing or almost clear during the study. Both treat-
ments demonstrated significant reductions in
erythema, scaling, and pruritus (p0.0001). Fur-
ther, patients treated with MAS064D who cleared
after 14 days of treatment were more likely to
remain clear than those using desonide cream
(p=0.0173). [Clin Dermatol 2009;27:S48-53]
Safety
MAS064D topical cream is generally well tol-
erated.
In the Veraldi pilot study, a 7-day course of
desonide 0.05 percent cream was available
for patients who experienced a flare during
the study period. None of the patients in the
MAS064D group required rescue medication
(versus 2 in the control group). In total, four pa-
tients (two each in the MAS064D and control
groups, respectively) reported a total of six mild
adverse events. [J Eur Acad Dermatol Venereol
2008;22:290-296]
Further, nine out of 10 participants of the
Elewski study rated the safety of MAS064D as
‘excellent.’ [Clin Dermatol 2009;27:S48-53]
Dosing
MAS064D cream should be applied three times
a day to the areas of the skin affected by SD.
Summary and conclusions
SD is a chronic, relapsing inflammatory der-
matological condition commonly encountered in
clinical practice. Multiple factors may contribute to
the etiology of SD, but it appears to be an interplay
between sebaceous activity, presence of Malasse-
zia spp and immune status. [J Eur Acad Dermatol
Venereol 2008;22:290-296] Topical and oral anti-
fungals, topical corticosteroids and immunomod-
ulating agents are cornerstones of SD treatments.
However, there are safety concerns with many of
these primary treatment options for SD.
MAS064D cream is a novel prescription non-
steroidal medical device approved by the US
Food and Drug Administration and for use in the
EU. The cream has antifungal and anti-inflamma-
tory actions. Emollients are important to relieve dry
skin and facilitate healing. The efficacy and safety
of MAS064D has been shown through animal tri-
als and randomized controlled studies.
This new treatment option is another addition
to the pharmaceutical armamentarium for patients
with mild-to-moderate SD.
35. JANUARY 2015 CALENDAR 35
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36. JANUARY 2015 HUMOR 36
“Yes Doctor Manolete,
you’re right.
It’s probably the full moon!”
“Have you been putting
on weight?”
“As far as l know he didn’t
die of anything. He was a
hypochondriac!”
“Any previous experience?”
“There’s nothing wrong in trying to blend in,
but why must you always mimic the behavior of
others?”
“I finally received your test results dear,
but before l let you read it,
l would like you to sign something for me!”
“With medical students, the only way for them to
learn, is to let them make their own mistakes! ”
![JANUARY 2015 2
ELVIRA MANZANO
There has been a progressive increase in
the incidence and prevalence of inflamma-
tory bowel disease (IBD) in Asia, characterized
by complicated disease behavior and signifi-
cant morbidity, says an expert at the recent Asia
Pacific Digestive Week conference held in Bali,
Indonesia.
“IBD has been traditionally known as a dis-
ease of the West and is relatively rare in Asia.
However, time trend studies from Japan, Korea
and Hong Kong have collectively shown a two-
to-three fold increase in the incidence and preva-
lence of IBD in the past 10 years,” said Professor
Siew Chien Ng from the Department of Medicine
and Therapeutics, Chinese University of Hong
Kong in Hong Kong.
In the first large scale population-based
study of IBD involving seven countries in Asia
(China, Hong Kong, Macau, Thailand, Malay-
sia, Singapore, Sri Lanka) and Australia, the
incidence of IBD varied from 0.54 to 3.44 per
100,000 individuals. China had the highest in-
cidence of IBD at 3.44 per 100,000. Ulcerative
colitis (UC) was more prevalent than Crohn’s
disease (CD), although the incidence of CD was
rapidly increasing in certain areas. [Gastroen-
terol 2013;145:158-165]
“Although family history of IBD was less com-
mon in Asia – as were extra-intestinal manifesta-
tions – complicated CD [penetrating, stricturing
IBD on the rise in Asia, most cases
reported in China
or perianal disease] was more common in Asia
than in the West,” said Ng.
In Hong Kong, for example, a study showed
the rate of perianal disease was 29.2 percent com-
pared with 15.8 percent in Australia (p=0.001). [J
Gastroenterol Hepatol 2012; 27:1266-1280]
“These changes may have been due to our
increased contact with the West, westernization
of diet, improved hygiene, increasing antibiotic
use, immune dysregulation and changes in the
gut microbiota,” Ng said. Asian patients with
CD have altered microbiota compared with their
Caucasian counterparts. Mucosa-associated mi-
crobiota in IBD may also differ geographically.
In a more recent population-based case-con-
trol study in Asia, where Ng was the principal in-
vestigator, breastfeeding, having pets and better
sanitary conditions were shown to be protective
of IBD, suggesting that childhood environment
plays an important role in modulating disease
development. [Gut 2014; pii: gutjnl-2014-307410.
doi: 10.1136/gutjnl-2014-307410]
The results, Ng said, highlight the importance
of childhood immunological, hygiene and dietary](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)