November 2013

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Sulfonylureas in the spotlight

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 2 November 2013

Sulfonylureas in the spotlight

Malvinderjit Kaur Dhillon

W
hen used as first-line therapy
for patients with type 2 diabetes
(T2D), sulfonylureas increase the
risk of death compared with standard first-
line metformin treatment, according to study
data presented at the 49th European Associa-
tion for the Study of Diabetes (EASD) annual
meeting recently held in Barcelona, Spain.
Lead author of the study, Professor Craig
Currie from Cardiff University’s School of
Medicine in Cardiff, Wales, urged physi-
cians to consider the potential hazard of
prescribing sulfonylureas in such a manner.
Currie and his team of researchers looked
at retrospective data extracted from the
Clinical Practice Research Datalink (CPRD),
a data set made up of more than 10 million
patients treated in primary care in the UK.
Findings from a retrospective UK study involving thousands of patients
Patients with T2D who were put on first-line with T2D suggest that sulfonylureas are linked to an increase in mortality
rate when used as first-line therapy.
glucose-lowering treatments between 2000
and 2012 were selected. The primary end-
point of the study was all-cause mortality. “There are significant differences between
The team identified 76,811 patients who the patients prescribed metformin and sul-
were treated with metformin monotherapy fonylurea at baseline and this will obvi-
and 15,687 with sulfonylurea monotherapy. ously explain the difference in mortality to
A matched-cohort study was performed an extent. However, the increased mortal-
comparing the two treatment groups after a ity in the sulfonylurea group remained af-
mean follow-up of 3 years. ter the data was adjusted with a Cox model
The analysis showed there were 3,209 in two different matching approaches base
deaths in the metformin group, while the on direct matching and propensity scoring
sulfonylurea group saw 2,172 deaths. This and in subgroup analyses. It didn’t matter
translated to 13.6 percent deaths per 1,000 if the patient was younger or older, male
person-years in the metformin group and or female, morbid or less morbid and well
44.6 percent deaths per 1,000 person-years controlled or poorly controlled. The hazard
in the sulfonylurea group. [Adjusted haz- ratios were all about the same,” said Currie.
ard ratio 1.58, 95% CI 1.48 to 1.68, p<0.001] “In my view, the safety of sulfonylureas
 3 November 2013
needs urgent evaluation because potentially
we are increasing the risk of all-cause mor-
tality,” said Currie.
In addressing questions on why sulfonyl-
urea is still being prescribed if there are sig-
nificant risks, Currie commented that this
is worrying as not all general practitioners
or other doctors are fully informed about
the risks of commonly used drugs.
He also noted that this particular data go
back to 2000, when the study was started.
Traditionally, patients were commonly pre-
scribed with sulfonylurea as first-line treat-
ment rather than with metformin.
Dr. Andreas Pfeiffer, of the Charité Uni-
versitätsmedizin, Berlin, Germany, said that
some patients switch to sulfonylurea as
they are unable to tolerate metformin and
that this is the case in about 15 percent of
diabetic patients.
Currie also discussed results from a sec-
ond study which compared 33,893 patients
who received second-line combination ther-
apy of sulfonylurea and metformin with
7,864 patients who were treated with a met-
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formin and DPP-4 inhibitor combination.
Analysis found that there were 16.9 per-
cent deaths per 1,000 person-years in the
sulfonylurea/metformin group and 7.3 per-
cent deaths per 1,000 person-years in the
metformin/DPP-4 inhibitor group.
“The DPP-4 inhibitors in combination
with metformin were safe compared to a
metformin and sulfonylurea combination,
the most common second-line glucose low-
ering regimen. I doubt the DPP-4s are ‘won-
der drugs’ but the difference in mortality
has more to do with sulfonylurea causing
an increase in insulin and other issues [car-
diovascular events],” said Currie.
It is interesting to note that in the Action
in Diabetes and Vascular disease: Preter-
Ax and DiamicroN Controlled Evaluation
(ADVANCE) study results, which were
announced at the 2008 EASD Congress in
Rome, the use of gliclazide modified-release
saw no increase in mortality in over 10,000
participants with T2D. This could suggest
that the type of sulfonylurea prescribed
might influence mortality risk.
 4 November 2013
Air pollution causes cancer, public health
expert calls for action
Greg Town
A
ir pollution is carcinogenic to hu-
mans and a leading environmental
cause of cancer deaths, according
to the International Agency for Research on
Cancer (IARC), a specialized cancer agency of
the World Health Organization (WHO), in a
recent announcement.
Leading experts convened by the IARC
Monographs Program found sufficient evi-
dence, based on an extensive evaluation of
the latest available scientific literature, to
suggest that outdoor air pollution is posi-
tively correlated with increased risks of lung
cancer and bladder cancer. [Lancet Oncology
2013; doi:10.1016/S1470-2045(13)70487-X]
Air pollution has already been linked to
an increased risk of various other chronic
diseases such as respiratory and heart dis-
eases. In recent years, exposure to air pollu-
tion has risen dramatically in some parts of
the world, especially in rapidly developing
countries with large populations. One study
in 2010 attributed 223,000 deaths from lung
cancer to air pollution. [http://www.iarc/fr/en/
publications/books/sp161/index.php]
The classification of air pollution as car-
cinogenic to humans is an important step,
said Dr. Christopher Wild, director of the
IARC. “There are effective ways to reduce
air pollution and, given the scale of the ex-
posure affecting people worldwide, this re-
port should send a strong signal to the inter-
national community to take action without
further delay.”
The predominant sources of outdoor air
pollution include transportation, station-
ary power generation, industrial and agri-
cultural emissions, and residential cooking
and heating. There are also natural sources
of air pollutants.
Commenting on the report, Professor Lee
Hin Peng, head of the Chronic Diseases Pro-
gramme at Saw Swee Hock School of Public
Health, National University of Singapore,
said: “The [carcinogenic] effects are due to
the multiple chemicals and particulate mat-
ter among the pollutants, leading to short-
term and long-term effects. Among the long-
term effects are asthma, obstructive lung
disease and lung cancer. So all relevant agen-
cies should be concerned and work together
to reduce production of such pollution.
“It is a matter of international concern,
not only because of the health hazards, but
also the harm to the environment,” he add-
ed. “We need to reiterate the message that
this is our only home, Earth, and we should
do all we can to protect its environment and
create cleaner air for all inhabitants.
“Promoting a green environment and
cleaner air are very important public health
objectives for all governments and relevant
public bodies to save Mother Earth for all
mankind,” said Lee. “We owe it to future gen-
erations to do our part, and we in the public
health fraternity have much to offer in terms
of further research and the development of
enlightened public policies to reduce pollu-
tion from all sources and to mitigate its del-
eterious effects.”
 5 November 2013 Forum
Mental health matters
Remarks by Dr. Margaret Chan, WHO director-general, at the launch of the Comprehensive
Mental Health Action Plan 2013-2020 in Geneva, Switzerland, on 7 October.
T
he Comprehensive Mental Health Ac-
tion Plan 2013–2020 is a landmark
achievement in many ways.
It focuses international attention on a long-
neglected problem, and it does so with a
welcome sense of urgency. It is a signal that
mental health deserves much higher strategic
priority. And it is a signal with an articulate
and unified voice behind it.
Rarely have I seen Member States work so
hard to get an action plan right and ensure
that its recommendations are workable and
on target.
Support came from countries with well-
established mental health services in place,
backed by legislation. But it also came from
countries that must balance the demands of
better mental health services with competi-
tion from other pressing priorities, including
HIV/AIDS, tuberculosis, malaria, and high
maternal and child mortality.
This tells us that mental health really mat-
ters.
The action plan is firmly rooted in the
principles of human rights, and draws sup-
port from a number of international conven-
tions that uphold human rights. This is also a
landmark achievement. As some of you have
noted in previous meetings of this Forum, the
treatment of people with mental and behav-
ioural problems remains cruel, inhuman, and
degrading in a number of countries.
The action plan calls for change. It calls for
change in the attitudes that perpetuate stigma
and discrimination. It calls for change in the
way services are delivered, and rightly so.
No country in the world can say that its
services are reaching all those in need, with
the most appropriate interventions, provided
with adequate social protection, and deliv-
ered in ways that promote social inclusion
and recovery.
The action plan calls for an expansion of
services, and it does so in ways that promote
greater efficiency in the use of resources. This
tells us that coverage can expand in austere
times if waste and inefficiency are reduced.
Major emphasis is given to the need to
redirect resources from mental hospitals to
smaller, community-based services that are
integrated into general health services. As
recommended, national action plans should
aim to provide outpatient services, supported
by an inpatient unit in all general hospitals.
Doing so facilitates the continuum of care,
comprehensive care of co-morbidities, and
better use of scarce human resources. Above
all, it helps normalize the management of
mental disorders and reduce the stigma and
discrimination that have isolated people with
these disorders since ancient times, leaving
them helpless and hopeless.
Recommended actions are sufficiently
simple and straightforward to facilitate im-
plementation on a large scale, yet also suffi-
ciently flexible to allow adaptation to national
priorities and specific circumstances, in any
resource setting.
By stressing the many opportunities for
greater efficiency, the action plan helps meet
 6 November 2013 Forum
the increased need for services at a time when
joblessness, homelessness, and hopelessness
affect so many in the current economic down-
turn.
The action plan aims to be comprehensive,
and it is, on many levels.
It is comprehensive in its approach, from
promotion and prevention to treatment, reha-
bilitation, care and recovery. Recent research
has given us the evidence, and the confidence,
to make the promotion of mental health and
the prevention of disorders a realistic and en-
tirely feasible objective.
The recommended life-course approach
facilitates the early detection of problems,
when rehabilitation and recovery often have
their greatest chance of success. Recommend-
ed actions are strongly evidence-based, with
emphasis on established risk factors and ap-
proaches that have been shown to work, es-
pecially in promoting rehabilitation and re-
covery.
Because the determinants of mental
health are so broad, the action plan is com-
prehensive in its engagement of numerous
non-health sectors, including education,
social welfare, labor, housing, and the ju-
diciary. It gives due credit to the tremen-
dous support provided by civil society or-
ganizations, including peer support from
patients’ associations.
The wide-ranging and inclusive scope is
readily apparent in the menu of policy options
for the implementation of recommended ac-
tions. Everything is there: from the inclusion
of services and essential medicines in health
insurance schemes, to programs to counter
bullying in schools, from yoga and medita-
tion, to the importance of mental health leg-
islation, from the dangers of over-diagnosis
and over-medicalization, to the importance of
information and monitoring.
We are well aware that many countries will
need technical support from WHO to imple-
ment the action plan. We are fully committed
to provide this support at all three levels of
the Organization, and are taking steps to en-
hance our capacity to do so.
Just as there is no health without men-
tal health, there is no progress without clear
benchmarks for measurement. And this is
what we all want to see: progress.
The action plan is not just visionary. For the
first time, Member States have set ambitious
global targets for monitoring levels of imple-
mentation, progress, and impact.
Think about what achieving these targets
will mean. By 2020:
• 8 0 percent of countries will have intro-
duced or updated a national plan for men-
tal health in line with international and re-
gional human rights instruments.
• H alf of all countries will have developed or
updated their mental health legislation to
protect human rights.
• S ervice coverage for severe mental disor-
ders will show a 20-percent increase.
• 8 0 percent of countries will have at least
two multisectoral programs for the promo-
tion of mental health and the prevention of
disorders.
• T he suicide rate will have gone down by 10
percent.
• And 80 percent of countries will be routine-
ly collecting and reporting on a core set of
mental health indicators.
The enthusiastic participation of so many
in the development of the action plan leaves
me confident that these targets can be reached.
Doing so will be a major step forward in giving
many millions of people hope and a chance
for a healthy life, in all its dimensions.
 7 November 2013 News
Even modest financial incentives can
impact health-promoting behaviors
Seah Yee Mey
O
ffering a financial incentive as little as
US$5 per week may motivate people
to exercise more, shows a Canadian
review.
Under the leadership of University of To-
ronto exercise psychologist Guy Faulkner
(Ph.D.), exercise physiologist Jack Goodman
(Ph.D.) and lead author Marc Mitchell (Ph.D.
candidate), a cardiac rehabilitation supervi-
sor at Toronto Rehabilitation Institute (TRI),
the researchers reviewed 11 randomized con-
trolled trials available through online data-
bases and published in English between 1980
and 2010. Patient sample sizes in the studies
ranged from 15 to 395, for a cumulative sam-
ple size of 1,453 adults.
Overall, the meta-analysis indicated that in
the short term, financial incentives increased
the amount of exercise in adults. While larger
incentives seemed to yield larger effects, even
a modest financial incentive produced posi-
tive results.
Other research has found that financial
incentive-based models for improving health
behaviors such as smoking cessation and
weight control have also shown favorable re-
sults in the short term.
“Our research suggests that … there is also
potential to drive long-term change, but that
will need to be studied further,” said Mitch-
ell. He explained that people’s actions gener-
ally serve their immediate self-interest at the
cost of long-term wellbeing. “The time com-
mitment and discomfort of exercise prevents
many adults from starting regular exercise.
For those who do start, most drop out within
6 months,” he said.
This study, published in the American Jour-
nal of Preventive Medicine, was primarily con-
ducted to investigate the conditions that might
increase cardiac rehabilitation adherence for
patients who either have had a cardiovascular
event or are at risk for cardiovascular disease.
Dr. Paul Oh, medical director of the Car-
diovascular Prevention and Rehabilitation
Program at TRI, said: “The financial incen-
tives model gives us an additional strategy to
help more people fully engage with the life-
saving care we provide.”
Oh said people who had previously expe-
rienced a major heart event can cut their risk
of dying from a second event by as much as
50 percent by participating in cardiac reha-
bilitation programs. However, there are pa-
tients who are either not receiving cardiac
rehabilitation or not sticking to the program
long term.
TRI will conduct a financial incentive-
based pilot study targeting patients who did
not complete the cardiovascular rehabilita-
tion program, as well as recent graduates.
“We want people to continue their exercise
regimen after graduating from cardiac rehab
…. The sustained behavior change we are
seeking could save our health system mil-
lions by preventing repeat heart events,” said
Mitchell.
 8 November 2013 News
Technovigilance saves lives
Angeline Woon
A
case study of a large English hospi-
tal has found that implementing an
electronic prescribing and decision
support system (ePDSS), a type of technovigi-
lance, reduces the rates of missed or delayed
medicine doses.
The hospital, which deals with acute care,
has an established ePDSS, which is used as a
warehouse of data on clinical activity and the
performance of clinical staff. Secondary data
is converted into intelligence about the perfor-
mance of individuals, teams and clinical ser-
vices, and improvements are made as needed.
Using the system, prescribing information
is entered electronically, and if patients miss
more than two doses of medication, such as
antibiotics, emails will automatically be trig-
gered. If no action is taken based on these
emails, the process will be escalated from
ward nurse onward through the hospital hi-
erarchy, ending with the chief executive.
The process was credited by the hospital in
the study with a substantial and sustained fall
in the rate of missed doses, from 12 percent
to 5 percent. The executive team of the hospi-
tal credited technovigilance with a “cultural
shift” in the attitudes of staff, especially when
it came to timely administration of medicine.
The study was published in the Milbank Quar-
terly [2013:91(3):424–54].
“This is one element of what we call ‘techno-
vigilance’ – turning data into intelligence which
can then be put into effective action. Other el-
ements include using the electronic system to
find examples of where care did not seem to
meet the required standards, and holding high-
level care omissions meetings with staff on
clinical areas to find out what happened,” said
lead author, Professor Mary Dixon-Woods, pro-
fessor of medical sociology at the University of
Leicester department of health sciences.
To obtain these findings, researchers per-
formed ethnographic observations of clinical
settings (162 hours) and meetings (28 hours)
at the hospital. They also had informal con-
versations with clinical staff, semi-structured
interviews with senior executives and collect-
ed documents relevant to the study.
“Data generated by the system are used to
make formerly hard-to-detect practices, be-
haviors and performance more transparent.
This means necessary preventative action can
be taken more easily,” said co-author Dr. Jamie
J. Coleman, of the University of Birmingham.
Some of these preventative actions included
improvements in medicine delivery and em-
phasis on the personal responsibility of staff.
However, technovigilance can lead to un-
intended consequences. “Technovigilance
is intentionally used as a way of ensuring
that individuals know their behavior is be-
ing monitored and that they will be open to
scrutiny. Although it’s not strictly intended to
be punitive, being called to a care omissions
meeting, for instance, could be a very uncom-
fortable experience for staff,” said Coleman.
Staff may also engage in ‘gaming’ in order
to create an appearance of good performance.
They may focus on the things that are mea-
sured by the electronic system at the expense
of other less measured, but important, activi-
ties such as patient communication. Another
area of concern is that the system seems to be
set up to monitor nurses’ behavior more than
others.
 9 November 2013 News
Stem cell therapy may halt cardiac
deterioration after heart attack
Priscilla Siew

S
tem cell treatment delivered via a patch
weeks after a myocardial infarction (MI)
attenuated further cardiac deteriora-
tion, preserved myocardial function and via-
bility, and increased microvascular perfusion
in a preclinical study involving rats.
The study showed similar positive results
to a previous investigation carried out by the
same team of researchers at the University of
Louisville’s Cardiovascular Innovation Insti-
tute in Louisville, Kentucky, US. In the pre-
vious study, stem cell treatment immediately
post MI preserved microvascular function
and left ventricle (LV) contractile mecha-
nisms.

‘‘
In a rat model of post MI, SCT delivered via a heart patch was highly
The clinical potential of an cardioprotective.

autologous patch... is high
In addition to showing effectiveness when
administered later in time after MI, the novel
heart patch delivery system used in the cur-
rent study was found to be a more efficient
method of delivery than injection, resulting in
a higher survival rate for the stem cells and
therefore more of them migrating into the
damaged tissue to create new blood vessels.
“Our cell patch [acts] as a ‘pause button,’
because once it was applied the heart didn’t
progress into worse function like the [control
groups],” said Dr. Amanda LeBlanc, who led
the research along with Dr. Stuart Williams,
the institute’s executive and scientific director.
Stromal vascular fraction (SVF) cells
were isolated from rat adipose tissue, plat-
ed on Vicryl, and cultured for 14 days. The
rats were randomly assigned to one of four
groups (n=9 per group): (a) 6-week MI treat-
ed with an SVF construct at 2 weeks (MI
SVF), (b) 6-week MI with Vicryl construct at
2 weeks (MI Vicryl), (c) 6-week MI untreated
(MI), and (d) 2-week MI (time point of inter-
vention). All endpoint parameters were as-
sessed at 2 or 6 weeks following initial MI
event.
The study found that Emax, an indicator of
systolic performance and contractile func-
tion, was lower in the MI and MI Vicryl
groups than in the MI SVF group, suggest-
ing that SVF treatment halted the progres-
sive worsening of LV function displayed by
10 November 2013 News
the untreated and control groups. Positron
emission tomography imaging revealed a
decreased percentage of relative infarct vol-
ume in the MI SVF group, versus MI and MI
Vicryl groups. Total vessel count and per-
centage of perfusion were both increased in
the infarct region of the MI SVF group, ver-
sus MI and MI Vicryl groups.
“This tissue engineering approach of cre-
ating an SVF-laden construct increases the
cell quantity that can be implanted into an
ischemic area without massive rates of acute
cell death and also improves cell retention
over time,” said the authors. “[The results]
indicate that treatment with an SVF con-
struct, either immediately or during the ac-
tive remodeling phase of scar formation post
MI, halts deteriorating cardiac function and
maintains LV viability and microcirculatory
perfusion.
“The clinical potential of an autologous
patch — that is, a patch seeded with the pa-
tient’s own stem cells — using adipose-de-
rived cells is high, as the patch may be used
in conjunction with existing heart attack
therapies to promote small vessel survival
and/or growth of new vessels following the
attack,” LeBlanc said.
11 November 2013 Conference Coverage
49th Annual Meeting of the European Association for the Study of Diabetes (EASD), September 23-27,
Barcelona, Spain
Diabetics living longer but CVD risk still high
Elvira Manzano
P
eople with type 1 diabetes (T1D) are
living longer now than ever before but
their risk of heart attack or stroke re-
mains higher than non-diabetics, according to
a large study in the UK.
“Advances in medical care are having
an impact on driving down mortality,” said
study author Dr. Helen Colhoun, professor of
public health at the University of Dundee in
Scotland. However, heart disease remains the
biggest killer in T1D, she added.
Colhoun and colleagues examined the life
expectancy and causes of death in patients
with T1D compared with the general popu-
lation. The study involved 24,971 individuals
aged ≥20 from the Scottish Care Information-
Diabetes Collaboration registry who were
diagnosed with diabetes between 2005 and
2008. [Abstract 301]
“The discrepancy in life expectancy between
diabetics and non-diabetics has hugely nar-
rowed from 27 years in the 1970s to 11 to14 years
in our study,” Colhoun said. Strategies to reduce
complications from diabetes might be working,
however a disparity still remains. More work is
needed to close the gap, she added.
Among diabetics, cardiovascular disease
(CVD) was the most common cause of death
at 25 percent. Thirty-seven percent of diabet-
ics aged ≥40 had blood pressure above conser-
vative targets (≥140/90 mmHg) and 39 percent
were not on a statin. By comparison, cancer
was the most common cause of premature
death among non-diabetics.
The incident rate ratio for all-cause mortal-
ity associated with T1D was similar in both
men and women (2.6 and 2.7 percent, respec-
tively; p<0.001) and decreased with age. At
age 20 to 24, diabetic men and women are liv-
ing 11 to 14 years less on average compared
with non-diabetics. Those aged 65 to 69 are
living 5 to 7 years less.
Poor glucose control poses a major problem.
For example, only 13 percent of diabetics in the
current study achieved the ideal HBA1c target
of <7 percent; 37 percent had very poor glyce-
mic control (≥9 percent.)
“It is difficult to get people with T1D to have
a good glycemic control without the risk of hy-
poglycemia,” Colhoun said. “We need to re-
think strategies for improving HbA1c. We need
greater emphasis on psychological care for dia-
betic patients and we need to increase the use of
insulin pump in our population.”
Importantly, T1D continues to be associated
with higher CVD and mortality compared with
the general population, said Colhoun. Aside
from blood pressure, attention must be paid to
other risk factors known to affect mortality such
as cholesterol and smoking.
We need more adjunctive therapies to help
patients achieve better glycemic control while
maintaining quality of life and preventing hy-
poglycemia. Risk factor management should be
improved and better treatment approaches are
needed to reduce the risk of CVD and prema-
ture death in this population, she concluded.
12 November 2013 Conference Coverage
49th Annual Meeting of the European Association for the Study of Diabetes (EASD), September 23-27,
Barcelona, Spain

Having kids lowers mortality risk in

patients with T1D
Rajesh Kumar

H
aving children lowers mortality in
people with type 1 diabetes (T1D),
according to the findings of a study
conducted in Finland.
In the study, researchers examined mor-
tality and causes of death among subjects
with childhood-onset T1D compared with
controls, with a focus on mortality differenc-
es between childless people and those who
had children.
The study included 5,162 people (45 per-
cent women) from the Finnish DERI (Diabe-
tes Epidemiology Research International) co-
hort who were diagnosed with diabetes at ≤17
years of age during the period 1965-1979, and
were placed on insulin at diagnosis.
Two non-diabetic controls for each person
in the DERI cohort were selected from the da-
tabase of the national Social Insurance Institu-
tion, and were matched for the year of birth,
geographical birth region and gender. Dur-
ing the follow-up until the end of 2010, 1,025
people with diabetes and 497 people without
diabetes had died.
All-cause mortality in people with diabe-
tes was significantly higher than that of con-
trol persons, both among men and women
(p<0.01). All-cause mortality was statistically
significantly lower in persons who had off-
All-cause mortality rates were significantly lower in T1D patients with
offspring.
spring (p<0.01), among both cases and con-
trols, and in both genders.
Among females, having children lowered
mortality in a similar way in diabetic persons
and controls (p=0.99 for interaction). Overall,
mortality was much higher in men than in
women, in both cases and controls. For people
with diabetes, the mortality differences be-
tween men and women were less pronounced
than among the controls, probably because
diabetes diminishes the difference between
genders.
“Although diabetes multiplies the mortal-
ity more in women than in men, it doesn’t
mean that the overall mortality of women gets
as high as that of men,” explained researcher
Dr. Lena Sjöberg of the University of Helsinki
in Helsinki, Finland.
13 November 2013 Conference Coverage
49th Annual Meeting of the European Association for the Study of Diabetes (EASD), September 23-27,
Barcelona, Spain
Big breakfast a healthy choice for T2D
patients?
Malvinderjit Kaur Dhillon
A
hearty breakfast rich in protein and fat
may be ideal for patients with type 2
diabetes (T2D) as it may help them to
achieve better glycemic and hunger control,
according to a study conducted in Israel.
This study was based on previous studies
which demonstrated that people who con-
sume breakfast regularly tend to maintain
a lower BMI than those who omit breakfast.
Studies have also shown that regular break-
fast eaters have more favorable fasting blood
glucose and post-meal insulin sensitivity.
[J Am Diet Assoc 2005;105:743-760, J Am Diet
Assoc 2005;105:1373-1382, Am J Clin Nutr
2005;81:388-396]
The study, co-authored by Professor Dan-
iela Jakubowicz of Tel Aviv University’s Sack-
ler Faculty of Medicine, looked at the effect
of a big breakfast and its composition on the
hormone profile of adults with T2D.
A total of 59 adult patients with T2D were
randomized in an open-label manner to low-
calorie diabetes diets consisting of either a big
breakfast (BB) or a small breakfast (SB). The
BB had a higher percentage of protein and
fat, making up about one-third of a patient’s
total daily energy intake, while the SB made
up 12.5 percent of their daily energy intake.
Of the enrolled participants, 47 completed the
study.
After 3 months, the BB group saw a three-
fold greater reduction in HbA1c levels com-
pared with the SB group (-4.62 percent ver-
sus -1.46 percent, p=0.047). The reduction in
systolic blood pressure was also significantly
lower in the BB group compared with the SB
group (-9.6 versus -2.4 mmHg, p=0.04).
About one-third of participants assigned to
the BB group were able to reduce their diabet-
ic medication dose, while about 17 percent in
the SB group had to increase their medication
dose. Those in the BB group also had lower
hunger scores, which meant they had better
levels of satiety, coupled with better levels of
fasting glucose.
“We conclude that a simple dietary manip-
ulation of a big breakfast diet rich in protein
and fat confers metabolic benefits compared
to conventional low-calorie diet in individu-
als with T2D. Meal timing and distribution
should be considered as important therapeu-
tic adjuvants to treat type 2 diabetic patients,”
said Jakubowicz.
“As the study progressed, we found that
hunger scores increased significantly in the
SB group while satiety scores increased in
the BB group. In addition, the BB group re-
ported a reduced urge to eat and a less preoc-
cupation with food and a greater urge to eat
over time. It is possible that a big breakfast
rich in protein causes suppression of ghre-
lin secretion, which is reflected in enhanced
satiety ratings,” said study co-author, Dr.
Hadas Rabinovitz of the Hebrew University
of Jerusalem.
Rabinovitz added that further research is
necessary to determine the mechanism by
which this seemingly simple diet approach
is beneficial compared with common dietary
approaches.
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15 November 2013 Conference Coverage
Gastro 2013 – Asian Pacific Digestive Week (APDW) / World Congress of Gastroenterology (WCOG),
September 21-24, Shanghai, China
Diagnosing functional dyspepsia difficult,
but simple tests can help
Radha Chitale
F
unctional dyspepsia’s general symptom
profile can make identification difficult
but a number of simple tests can help
to distinguish it from other, often concurrent,
gastrointestinal diseases.
Functional dyspepsia (FD) involves one or
more of bothersome feelings of fullness after
eating, early fullness, or epigastric pain or
burning, without the presence of overt dis-
ease that might explain symptoms.
Gastroesophageal reflux (GERD) disease or
irritable bowel syndrome can occur at the same
time as FD but diagnosis of either of these does
not exclude FD diagnosis. And even when FD
diagnosis is made, treatment procedures can
be trial-and-error. Refractive FD patients tend
to be put on antidepressant therapy.
“If you don’t have response with your
first choice of therapy, it has been suggested
to add on or switch to another therapy, and
then go to antidepressants in the refractory
patients,” said Dr. Jan Tack of the University
of Leuven in Leuven, Belgium. “And there is
not a lot of solid evidence to justify this.”
Understanding the pathophysiologi-
cal abnormalities of FD can help determine
treatment choice and predict how patients
will fare 2-3 years down the line, Tack said,
but it can also help obtain a more patient-ac-
ceptable diagnostic label, which can reduce
patient stress.
Additional testing can also help exclude
with better certainty any other diagnoses for
refractory FD.
Among the myriad tests that can be ad-
ministered, examining the cause of reflux
and potential overlapping diseases is most
useful as it is often a symptom of GERD as
well. [Gastroenterology 1997;112:1448-1456]
“The heartburn picture is useful in clini-
cal practice,” Tack said. “But therapeutic im-
plications are limited when meta-analyses
show no dose-response effects from proton
pump inhibitor therapy [for acidity] in dys-
peptics. So perhaps giving a higher dose of
proton pump inhibitors to a pre-identified
group might help. Going further to anti-re-
flux surgery is a risky scenario.”
Upcoming, Tack said, is the gastroparesis
breath test, which involves eating a meal that
contains a small amount of radioactive ma-
terial after which breath samples are taken
over time to see how efficiently the stomach
is emptying its contents. Delayed emptying
is associated with FD.
More invasive tests such as endoscopies
or biopsies might reveal malignancies, ul-
cers, celiac disease, and other issues less than
10 percent of the time, but because they are
serious, Tack said they are worthwhile. Still,
less invasive CT scans are preferred.
“There is clearly an area of uncertainty
where we’re willing to switch therapy or add
antidepressants,” Tack said. “This is proba-
bly the grayest place for initial testing… and
perhaps the pathophysiological tests to look
at are intragastric pressure as a surrogate in
terms of organic testing, repeat endoscopy,
biopsies and ultrasounds.”
16 November 2013 Conference Coverage
Gastro 2013 – Asian Pacific Digestive Week (APDW) / World Congress of Gastroenterology (WCOG),
September 21-24, Shanghai, China
Preventing opportunistic infections in IBD
Rajesh Kumar
P
hysicians should aim to reduce and pre-
vent serious opportunistic infections in
patients with inflammatory bowel dis-
ease (IBD) through screening at the time of
diagnosis and before starting immunomodu-
lating or anti-TNF therapies, according to the
second European evidence-based consensus
on the prevention, diagnosis and manage-
ment of opportunistic infections in IBD.
The immunomodulators commonly used
in IBD and associated with an increased risk
of opportunistic infections include thiopu-
rines, methotrexate, calcineurin inhibitors,
anti-TNF agents and other biologics, said co-
author Dr. Fernando Magro of the Depart-
ment of Pharmacology and Therapeutics at
the Faculty of Medicine, University of Porto,
Porto, Portugal.
Elderly patients and those with a history
of serious infections are particularly sus-
ceptible, as are those with congenital im-
munodeficiency, leukemia, lymphoma, HIV,
hyposplenism and renal failure and those
undergoing therapy with alkylating agents,
antimetabolites, radiation or large doses of
corticosteroids (≥20 mg/day of prednisolone
for 2 or more weeks), said Magro.
Opportunistic infections are usually pro-
gressive infections by microorganisms that
have limited or no pathogenic capacity under
ordinary circumstances, but which can cause
serious disease as a result of the predispos-
ing effect of another disease or its treatment.
At diagnosis of IBD, patients should be
screened for history of susceptibility to prima-
ry varicella zoster virus (VZV) infection. Those
without a history of chicken pox, shingles or
receipt of two doses of varicella vaccine should
be tested for VZV antibodies, Magro added.
Regular gynecologic screening for cervical
cancer is strongly recommended for women
with IBD, especially if they are treated with
immunomodulators. Young immunocom-
promised women are advised to obtain a Pap
test twice in the first year after diagnosis and,
if the results are normal, annually thereafter.
“[Similarly], patients with positive hepa-
titis B core antibody (HBcAb) and negative
surface antigen (HBsAg) may have occult
HBV infection. Reactivation of occult HBV
rarely occurs with immunosuppressive
therapy used in IBD. Still, viremia should be
assessed every 2 to 3 months, but anti-viral
therapy is not recommended unless HBV
DNA is detected,” said Magro.
All patients with IBD are recommended
hepatitis A vaccination before travel to en-
demic areas, but response to immunization
should be checked by serological essay. Rou-
tine prophylactic HPV vaccination is also
recommended and current or past infection
with HPV is not a contraindication for im-
munomodulator therapy, he said.
Adults aged ≥19 years with immunocom-
promising conditions who have previously
received pneumococcal conjugate vaccine
13 (PCV13) or pneumococcal polysaccharide
vaccine 23 (PPSV23) should receive a dose of
PCV13 first, followed by a dose of PPSV23
at least 8 weeks later. A second PPSV23 dose
is recommended 5 years later. Those with
previous vaccination with PPSV23 should
be given a PCV13 dose ≥1 year after the last
PPSV23 dose, Magro concluded.
 Novel Treatments
in the Management of
Rheumatoid Arthritis

Professor Josef Smolen Professor Robert Moots Dr Chi-Chiu Mok

talks about early intervention discusses how treatment has shares his perspectives on
and treatment targets in evolved for patients with overcoming the challenges
rheumatoid arthritis rheumatoid arthritis and the and issues in the management
importance of compliance of rheumatoid arthritis in Asia

MIMS Video Series features

interviews with leading experts
In this Series, find out what these experts have to say about the importance of early
diagnosis of rheumatoid arthritis, their perspectives on overcoming compliance
issues and updates on novel treatments.

For A 5-minute Update

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18 November 2013 Conference Coverage
Aesthetics Asia 2013 Exhibition & Congress, September 12-14, Singapore
Testosterone deficiency a concern in Asia
Laura Dobberstein
A
sian men have similar rates of bio-
chemical andropause comorbidities
and associated risk factors as those in
the US and other Western countries, says an
expert.
“We all know that testosterone falls as we
grow older, especially in gentlemen,” said
Dr. Caroline Low of Drs Jiten & Caroline
Medical Centre + X-ray, Singapore. Low was
speaking on the topic of guidelines for tes-
tosterone therapy in adult men at the recent
Aesthetics Asia Exhibition and Congress
2013 held in Singapore.
In a 2006 US study of 2,162 men over the
age of 45 who visited participating doctors
for any reason, 38.7 percent had a biochemi-
cal diagnosis of andropause defined as total
testosterone levels below 300 ng/dL. Odds
ratios for testosterone deficiency were sig-
nificantly higher in men with hypertension
(1.84), hyperlipidemia (1.47), diabetes (2.09),
obesity (2.38), prostate disease (1.29) and
asthma or COPD (1.4) than in men without
these conditions. [Int J Clin Pract 2006;60:762-
769]
The 2006 Subang Men’s Health Study
found 19.1 percent of 4,000 Malaysian men
aged between 40 and 80 years had a biochem-
ical diagnosis of andropause. The prevalence
of metabolic syndrome among the study
population ranged between 29.6 percent and
32.9 percent. [Asian J Androl 2006;8:506]
To diagnose testosterone deficiency, Low
recommended identifying compatible symp-
toms through a medical history and physical
examination, excluding diseases with similar
symptoms including depression and anemia,
and performing a biochemical confirmation.
A 2004 Australian study of androgen-de-
ficient men showed that 69 percent experi-
ence a loss of energy, 35 percent have a di-
minished libido, 38 percent experience lack
of motivation, 40 percent have a cantanker-
ous mood, 33 percent are sleepy after lunch,
16 percent have an inability to concentrate,
12 percent experience hot flushes, 40 percent
have slow beard growth, and 12 percent suf-
fer from muscular aches. [J Clin Endocrinol
Metab 2004;89:3813-3817]
Patients typically come to Low with signs
of depression, non-sociable behavior, panic
attacks, an inability to put on muscle and a
simple complaint of feeling “old.”
Current testosterone therapies range from
short-acting (2 to 4 weeks) to long-acting (12
weeks). For Asian men, Low said she pre-
fers oral pills or injectables to prevent inter-
mittent medication use with creams, and to
avoid embarrassment from the daily shav-
ing of the scrotum required for patches. Al-
though price is important when selecting a
treatment method, Low pointed out that the
prices among testosterone replacement ther-
apies are similar when compared on a per
week basis.
The first improvement typically seen in
Low’s patients is a fall in fatigue levels, fol-
lowed by a decrease in depression and an
increase in sociability after 3 weeks of treat-
ment. Those undergoing testosterone treat-
ments are known to also experience an in-
19 November 2013 Conference Coverage
crease in bone mineral density, lean body
mass, erythropoiesis, physical activity, men-
tal activity, mood, cognitive abilities, libido,
and quality of life. Aggressiveness generally
does not change in Low’s patients.
Those receiving testosterone replacement
therapy may initially have a worsening of
sleep apnea, especially if the patient is obese,
said Low. Other risks include a decrease in
fertility, a rare but existing chance of poly-
cythemia and a contraindication for prostate
cancer.
Low described a need for competent phy-
sicians managing andropause and for well-
informed patients committed to follow-up
and careful monitoring.
“At the end of the day, testosterone is not
a fountain of youth,” said Low. “We want to
prevent the preventable and delay the inevi-
table.”
20 November 2013 Conference Coverage
European Respiratory Society Annual Congress 2013, September 7-11, Barcelona, Spain
Telemedicine offers viable option for
management of some TB patients
Rajesh Kumar
T
elemedicine may offer a useful alterna-
tive for treatment supervision in some
hard-to-manage tuberculosis (TB) pa-
tients who require directly observed treat-
ment (DOT), a pilot study has suggested.
DOT is recommended for geographically
isolated or socially or clinically complex cas-
es of TB, including drug addicts or homeless
people, who may be unable or unwilling to
visit a clinic. But it is often time-consuming
for patient and is resource-intensive for the
outreach clinics.
UK researchers initiated a virtually ob-
served treatment (VOT) program that re-
quired patients to email their heatlthcare
provider with a short video clip showing
themselves taking their medication using a
smartphone or laptop.
Nine of the 17 patients who needed to
take their medication more than once a day
but were unable to receive DOT, had refused
DOT, or had transportation difficulties get-
ting to the clinic, eventually started on the
program.
The patients were provided a laptop or
smartphone and trained in how to take a
video of the pills in their hands, swallowing
the pills, and an open mouth afterward to
show no pills left; and how to email those
clips.
Seven patients returned video clips, six of
them for a minimum of 95 percent of the treat-
ment encounters. At the end of 6 to 8 months,
three patients cleared TB and completed
treatment on VOT, while the rest are soon ex-
pected to.
“[About] one in three individuals who
would require DOT, I think, would succeed
with VOT. It is not perfect for everyone but it
does seem to be effective,” said researcher Dr.
Marc Lipman of the University College Lon-
don, England.
Through virtual monitoring of patients,
healthcare professionals can ensure effective
medication use without the need for a one-to-
one session. Telemedicine has the potential to
not only reach people who are otherwise un-
engaged, but also reduce costs and resources,
the researchers said.
Incidentally, the enrolled patients were
thought to be at low risk for selling or losing
the smartphones and laptops, although many
of the 17 did just that. When asked about this,
Lipman said the cost of generic smartphones
is falling drastically and the cost savings from
the successfully treated patients were still po-
tentially much higher.
“If you’ve got a complex patient, by and
large you get them through treatment, but the
cost associated with it is something like 25 to
50 times the standard TB treatment cost, just
because they are so resource-intensive,” he
said.
A planned larger randomized controlled
trial comparing VOT with DOT will also ex-
plore the cost-effectiveness of the telemedi-
cine option.
21 November 2013 Conference Coverage
European Respiratory Society Annual Congress 2013, September 7-11, Barcelona, Spain
Severe asthma may be less responsive to
steroids
Elvira Manzano
P
atients with severe asthma are less like-
ly to respond to treatment with steroids
than those who have a mild or moder-
ate form of the disease, preliminary data from
the U-BIOPRED* study suggest.
The first analysis of data from a cohort of
470 adult patients with asthma – 372 with se-
vere asthma and 98 with mild-to-moderate
asthma – and 100 healthy subjects showed
that 44.4 percent of those with severe asthma
still experienced exacerbations and severe
symptoms despite taking high doses of corti-
costeroids. [Abstract 3029]
“A significant proportion of patients with
severe asthma require oral corticosteroids as
maintenance therapy; however this group
may be insensitive to the anti-inflammatory
effects of corticosteroids,” said principal in-
vestigator Dr. David Gibeon, clinical research
fellow at Airway Division, Imperial College
and honorary respiratory registrar at the Roy-
al Brompton Hospital in London, England.
“There’s a clear unmet need for this group of
patients.”
Compared with patients who have mild or
moderate disease, patients with severe asth-
ma had greater airway obstruction (FEV1, 66
percent) and higher proportion of eosinophils
in the sputum (median SpE count, 2.8 percent
[IQR, 0.4-14]), which is a marker of airway in-
flammation. They were also more likely to be
female, with nasal polyps, eczema, hay fever
and gastro-esophageal reflux disease (GERD);
with higher body mass index (BMI), impaired
lung function and greater airway inflamma-
tion that required more asthma medications.
Additionally, the increases in sputum eo-
sinophils observed in severe asthmatics cor-
related with increases in fraction of exhaled
nitric oxide (FeNO) in their breath. There
were also interesting differences with regard
to sputum inflammatory phenotype – pa-
tients on steroids had more cellular sputum,
whereas the non-steroid group were pauci-
granulocytic.
Because asthma manifests differently in
each individual, responses to treatments also
vary hugely. Currently, there are not too many
medications for severe asthma. The only bio-
logic available is anti-IgE therapy which may
be suitable for a significant proportion of se-
vere asthmatics but does not work in all cases,
Gibeon said. “U-BIOPRED aims to tackle this
problem. This analysis of associated lipido-
mic, transcriptomic and proteomic data will
improve our understanding of severe asthma
phenotypes and ultimately aid drug develop-
ment.”
U-BIOPRED project lead Professor Peter
Sterk from the University of Amsterdam, The
Netherlands, said the project will take them a
step closer to developing personalized treat-
ment for asthma and will serve as an instru-
ment for improved medical practice.
The 5-year study will collect over 3 million
samples from 1,028 adult and pediatric pa-
tients with asthma. Full results are expected
in 2014.
*U-BIOPRED: Unbiased biomarkers in prediction of respiratory disease
outcomes
a MIMS publication

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Continued
on page 2
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23 November 2013 Conference Coverage
European Respiratory Society Annual Congress 2013, September 7-11, Barcelona, Spain
Breath test sniffs out lung cancer
Elvira Manzano
A
simple breath test may sniff out lung
cancer and classify severe asthma ac-
cording to phenotypes, two prelimi-
nary studies suggest. If true, this could pave
the way for an inexpensive and non-invasive
screening method.
Researchers used electronic nose (eNose)
sensors to characterize the volatile organic
compounds (VOCs) expressed in the exhaled
breath of patients with lung cancer and other
lung diseases.
The first trial looked at breath samples
from 474 patients with lung cancers and other
chronic lung conditions (asthma, pneumonia,
bronchiectasis) and healthy volunteers. Of
those patients, 210 were non-smokers and 265
were smokers. [Abstract P2889]
The eNose was able to accurately iden-
tify 128 of 140 cases of lung cancer in non-
smokers (positive predictive value [PPV],
91.4 percent) and 114 of 121 cases in smok-
ers (PPV, 94.2 percent). Similarly, the device
ruled out cancer in 120 of 125 healthy volun-
teers and in 84 of 89 smokers. The average
negative predictive value was 95 percent in
both groups.
Overall, the eNose had an average sensitiv-
ity of 96 percent in detecting lung cancer. Av-
erage specificity was 91 percent.
“These are good findings,” said lead au-
thor Dr. Maris Bukovskis from the University
of Latvia in Riga, Latvia. “Analyzing exhaled
breath by eNose has several advantages... it is
cheap and non-invasive, is easy to do and is
sufficiently accurate as an initial screen.”
The next step, he said, is to expand trials to
a wider sample of patients to determine if it is
effective for clinical use.
In the second trial involving 57 patients
with asthma, unbiased fingerprinting by the
eNose provides three different clusters that
can identify severe asthmatics with respect
to inflammation and lung function. [Abstract
3041]
Although it will take years before the device
can be used in the clinic, ERS president-elect
Professor Elizabeth Bel from the Academic
Medical Centre, Amsterdam, said it will be in-
teresting to see the day when clinicians could
diagnose adenocarcinoma or squamous cell
carcinoma based on a simple breath analysis.
“That should be the ultimate goal.”
Previous studies have shown that dogs and
mice make ideal cancer detectors. Researchers
nevertheless may find it better working with
the eNose than with animals.
Currently, investigators are training the
eNose to pick up the pattern of chemicals
given off by cancers and other diseases and
to distinguish between odors to prevent false
positives and false negatives.
24 November 2013 Conference Coverage
European Respiratory Society Annual Congress 2013, September 7-11, Barcelona, Spain
New rapid diagnostic tests for drug-
resistant TB
Rajesh Kumar
T
hree new diagnostic tests could each
be used to successfully diagnose drug
resistance in tuberculosis (TB) patients in
a quarter of the time taken by current methods.
In a study, the tests took anywhere from
5 to 15 days to complete, compared with the
gold standard mycobacteria growth indicator
tube (MGIT) drug susceptibility testing with
sputum culture that can take from 21 days to
as long as 3 months. [Abstract 188]
If perfected, each of the new tests could
serve as an effective alternative to the gold
standard, increasing the possibilities open to
clinicians, said the researchers.
They analyzed pyrosequencing (PSQ; a
DNA sequencing technique); Hain line probe
assay (LPA; a commercial test that detects ge-
netic mutations in the bacteria) and the mi-
croscopic observation drug susceptibility test
(MODS; which screens samples under the mi-
croscope) and investigated their effectiveness
in over 1,000 patients in India, Moldova and
South Africa.
The standard test was performed along-
side the new tests to evaluate their efficacy
in diagnosing resistance to several TB drugs
(isoniazid, rifampin, moxifloxacin, ofloxacin,
amikacin, capreomycin, and kanamycin).
The MODS test took 15 days to complete,
PSQ took 8 days and the LPA 5 days. All three
tests produced the same results as the stan-
dard testing – 95 to 98 percent of the time for
almost all the drugs.
“Our findings suggest these three tests
could provide a quicker way to identify pa-
tients who need alternative treatment regi-
mens,” said Professor Antonino Catanzaro
from the University California, San Diego,
California, US.
PSQ was the most expensive and most dif-
ficult to perform, MODS was the slowest but
cheapest, and the LPA, already approved in
Europe, fared somewhere in the middle, said
Catanzaro.
It also took as long as 280 days for some
samples owing to technical glitches in per-
forming it, but Catanzaro said the researchers
are working to resolve that, after which the
test could theoretically “give results within
one hour.”
Drug susceptibility tests are carried out
in people with active TB in order to identify
which drugs the TB bacteria are sensitive or
resistant to.
It is essential that these are identified as
early as possible so that the patient can be pro-
vided with the most effective treatment, and
therefore the most rapid cure, and to prevent
the development of even more drug-resistant
TB. This is particularly important for patients
with extensively drug-resistant TB (XDR-TB),
who may have a short life expectancy if not
treated properly.
The WHO has mandated the development
of new tests to reduce the average diagno-
sis time of XDR-TB from months to about a
week.
25 November 2013 Conference Coverage
17th World Meeting of the International Union of Phlebology, September 8-13, Boston, Massachusetts, US
Determining outcomes in large leg ulcers
Radha Chitale
U
lcer duration, compression treatment
and the rate of successful skin graft-
ing are three key factors that deter-
mine how well and quickly large vascular ul-
cers will heal, a new study shows.
“There is still no consensus on risk fac-
tors for healing and recurrence in surgically
treated [leg ulcer] patients,” said lead re-
searcher Dr. Stanislava Tzaneva of the Medi-
cal University of Vienna in Vienna, Austria.
“Early performed split skin grafting shaving
in patients with large and very large vascular
ulceration enhanced healing, and by cutting
down the ulcer duration, reduced the ulcer
recurrence.”
Venous leg ulcers are the most common
type of ulcer, particularly in older people, and
chronic venous leg ulcers affect about 1 per-
cent of the population. These open wounds
occur because of increased blood pressure
in the leg veins from damaged valves and
gravity.
Seventy-percent of patients who experi-
ence venous leg ulcers also have other venous
disorders. Arterial disease tends to be com-
mon, occurring in about 40 percent of pa-
tients. Large ulcers are over 10 cm2 and heal
slowly.
Removing the ulcerated skin and some of
the surrounding dermis (shave therapy) and
grafting on new skin comprising the epider-
mal and part of the dermal layer (split-thick-
ness skin graft) is the standard treatment for
such ulcers and is effective. Tzaneva’s study
investigated which factors optimized efficacy.
The retrospective study included 61 ulcers
from 61 patients with split skin grafted ulcers
at an Austrian facility between 2001 and 2009.
The ulcers were large or very large, greater
than 10 cm2, and had not healed over 2 months
of conservative treatment. Some ulcers had
persisted for nearly 3 years. Fifty-percent of
patients suffered from deep venous reflux.
Patients underwent another shaving and
split skin grafting procedure as well as cor-
rectional surgery for vascular insufficiencies,
which included stripping endovascular laser
ablation, dissection or stripping of insufficient
veins, and arterial reconstruction.
Eighty-three percent of ulcers healed after
a mean 1.9 months.
After 3 months of follow-up, about 70 per-
cent of ulcers healed completely and 80 per-
cent healed after 6 months. Two patients had
a prolonged healing process that finished af-
ter 12 and 30 months, respectively.
Among the risk factors for ulcer heal-
ing, ulcer duration (hazard ratio [HR] 0.990,
p=0.042), compression treatment (HR 2.024,
p=0.016) and the rate of immediate graft take
(p<0.001) were found to be significant. Com-
pression treatment appeared to be the most
significant as it more than doubled the likeli-
hood of healing, Tzaneva said.
Recurrence occurred in 25 percent of healed
ulcers after a mean 14 months, but, more im-
portantly, two-thirds of recurrent ulcers re-
curred within 12 months.
Male sex (HR 0.140, p=0.02), ulcer duration
26 November 2013 Conference Coverage
(HR 0.982, p=0.046), and deep venous reflux
(HR 5.395, p=0.02) were the most significant
factors associated with recurrence.
Tzaneva said there was no explanation
for why men fared worse than women in
recurrent ulcers but the more than five-fold
increased risk associated with deep venous re-
flux suggests that vein surgery, which can be
performed concurrently with split skin graft-
ing, can help improve healing and reduce the
risk of recurrence, especially if intervention is
early.
27 November 2013 Conference Coverage
17th World Meeting of the International Union of Phlebology, September 8-13, Boston, Massachusetts, US
Still little consensus on deep venous reflux
and obstruction treatment
Radha Chitale
A
  targeted survey among venous dis-
ease experts showed heparin and
compression remain popular choices
for treating deep venous disease, but treat-
ment recommendations still varied widely
overall and highlighted the need for greater
consensus.
“Preferred management options with
complex venous reflux and obstructions are
various across the world and a consensus
would be valuable to determine the best man-
agement options,” said lead researcher Ms.
Hayley Moore, of the Academic Section of
Vascular Surgery at Imperial College London
in the UK.
Venous disease affects about 15 percent of
the adult population and even more in some
countries – 30 percent of adults in the UK, for
example. Deep venous disease is present in a
significant portion of these patients and treat-
ment can be a lengthy, expensive process.
“Despite all the recent advances in superfi-
cial venous disease, which can be easily treat-
ed with surgery or endovenous methods, in
deep venous disease, the treatment options
are limited to compression and elevation or
surgery, which is often invasive for patients
with multiple comorbidities,” Moore said.
To establish current trends in deep venous
disease management, Moore and colleagues
analyzed data from a survey of 112 experts
asked to suggest the best management strat-
egy for five patients with complex venous
obstruction and five patients with either com-
plex venous reflux or combined reflux and
obstruction.
The complex venous obstruction scenarios
received 77 responses and the reflux and ob-
struction scenarios received 35.
Among the complex venous obstruction
scenarios were cases of patients with acute
deep vein thrombosis, subclavian veins, and
inferior vena cava occlusion. Anticoagulation
therapy with heparin was consistently the top
choice among a majority of responses, though
sometimes warfarin was selected also. More
invasive procedures such as catheter directed
thrombolysis, open thrombectomy and stent-
ing were significantly less popular.
Compression was by far the most preferred
way to treat venous reflux or obstructions and
was selected between one- and three-quar-
ters of the time. The remainder of responses
tended to be split between anticoagulation
therapies, open surgery, pharmacomechani-
cal thrombolysis, veinography, and stenting.
In combined reflux and obstruction cases,
Moore noted that treatment of obstruction
was almost always the first choice while sur-
gery for deeper veins was generally a second-
line option.
28 November 2013 Conference Coverage
17th World Meeting of the International Union of Phlebology, September 8-13, Boston, Massachusetts, US

Monitoring, reversibility remain biggest

challenges with new oral anticoagulants
Radha Chitale

N
ew oral anticoagulants (NOACs),
such as dabigatran, apixaban and
rivaroxaban, may offer more and,
in some cases, better treatment options for
patients at risk of blood clots, but concerns
over difficulties in monitoring anticoagula-
tion or reversing excess bleeding led doctors
to advise caution in their use and to select ap-
propriate candidates for these new therapies
carefully.
“NOACs have many appealing aspects of
clinical use,” said Dr. Stephanie Dentoni, of
the California Vein and Vascular Institute in
Stockton, California, US. “But don’t forget
about good old low-molecular-weight hepa-
rin and warfarins. When you have someone
on a regular dose, taking it as they should be
taking it, they are good anticoagulants.”
Prior to the approval of the NOACs, vita-
min K antagonists such as warfarin were the
only oral anticoagulants available for use in
preventing and treating venous thromboem-
bolism, for example, or for stroke prevention
in atrial fibrillation. While effective, warfarin
While new anticoagulants do not require monitoring, they still carry risks
requires extensive monitoring for dosages according to an expert.
and drug interactions. Intravenous therapies
like heparin can be inconvenient for patients. cluding bleeding, venous thromboembolism,
A number of trials over the last decade, how- heart attack, stroke and other major vascular
ever, have demonstrated either noninferiority events. [Thrombosis 2012;2012:108983]
or superiority of NOACs compared with stan- Unlike traditional anticoagulants, NO-
dard anticoagulation therapy for outcomes in- ACs do not require monitoring, have fixed
29 November 2013 Conference Coverage
doses and predictable dose responses, Den-
toni said. They can also be given as mono-
therapy.
But the new agents still carry risks. Dr.
Jawed Fareed, director of the Hemostasis and
Thrombosis Research Program at Loyola Uni-
versity Medical Center in Maywood, Illinois,
US, noted that some trials showed an increased
risk of myocardial infarction with dabigatran.
In addition, they are single-target drugs and
do not have the anti-inflammatory properties
of heparins and older anticoagulants.
And the biggest concern for Fareed, Den-
toni and colleagues was that NOACs cannot
be monitored and there is no reliable way to
reverse bleeding should it occur.
Warfarin, for example, is reversible with
infusions of vitamin K.
“If you do have somebody you think may
be failing these medications, you can’t check
to see if they have adequate anticoagulant ef-
fect on board,” Dentoni said. “They may have
missed doses and not told anyone or they
may have blood clots and you don’t know if
it’s a failure of the medications or a failure of
the patient taking the medications.”
READ JPOG ANYTIME, ANYWHERE.
Download the digital edition today at www.jpog.com
Dentoni said judicious application of these
new agents will be important as doctors con-
sider their use in patients, especially as they
are not interchangeable drugs. Dabigatran is
a thrombin inhibitor while apixaban and riva-
roxaban are anti-factor Xa agents.
NOACs could be useful in patients with
documented warfarin failure. Susan Kahn
said younger, healthier patients in need of
an anticoagulant for surgery-associated DVT
are more likely to choose a new agent for con-
venience.
Where NOACs will not be useful is in in-
terventional and surgical applications owing
to the possibility of uncontrolled bleeding
complications, said Fareed.
But Dr. Malay Patel, a vascular surgeon in
Ahmedabad, Gujarat, India, said many ex-
perts anticipate that research over the next
few years will make reversal of NOACs easi-
er, though until then their use will be limited.
There is already some evidence the new
agents, dabigatran in particular, may be
reversible with prothrombins and hemodialy-
sis, but that remains an area of active investi-
gation.
30 November 2013 Feature
Clamping the cord after delivery – how
soon is too soon?
Dr. Tan Eng Loy
Consultant, Department of Obstetrics & Gynaecology,
Singapore General Hospital, Singapore.
D
elayed cord clamping – or waiting
for 2 to 3 minutes after the delivery
of an infant before clamping and
cutting the umbilical cord – is believed to
give the newborn more iron reserves thereby
lowering the risk of anemia, according to a
Cochrane review of 15 trials. [Cochrane Da-
tabase Syst Rev 2013, doi: 10.1002/14651858.
CD004074.pub3]
The review, which analyzed data from
3,911 women and infant pairs, said that dur-
ing the time the cord isn’t clamped, blood con-
tinues to pulse from the placenta to the baby
until the pulses naturally stop around 3 min-
utes. An extra volume of blood resides in the
placenta at birth, and placental transfusion
sends this blood back to the baby, to prepare
and support the fetal organs to transition to
breathing on its own. It provides an adequate
number of red blood cells to then transport
oxygen throughout the baby’s body.
The advantages are apparently not just for
full-term babies, but for ‘preemies’ as well–
improved motor development and a lower
incidence of intraventricular bleeding, which
can lead to brain damage. Medical Tribune
(MT) interviewed Dr. Tan Eng Loy (TEL), a
consultant with the Department of Obstetrics
& Gynaecology at Singapore General Hospi-
tal, on this subject.
31 November 2013 Feature
MT: Is delayed cord clamping truly capable
of all the advantages mentioned above?
TEL: Delayed cord clamping results in a high-
er concentration of red blood cells in the new-
born baby, especially if the baby is held below
the level of the undelivered placenta.
This is due to blood in the placenta being
transferred back to the baby since blood flow
in the umbilical cord vessels can continue
for several minutes after a baby is born. For
a baby delivered at term, this equates to the
baby receiving an additional 80-100mL of
blood. This translates to an extra 20-30 mg/
kg of iron, an amount that is sufficient for the
baby for about 3 months.
However, the increase in red blood cells
from delayed cord clamping is associated
with a significant increase in the baby requir-
ing phototherapy for jaundice (when the red
blood cells are broken down).
For the pre-term baby, delayed cord clamp-
ing is associated with lower requirements for
transfusion for anemia, lower risk for necro-
tizing enterocolitis, and fewer infants with ev-
idence of intraventricular hemorrhage (IVH)
or bleeding on ultrasound. The long-term sig-
nificance of ultrasound finding of IVH is not
yet known. No significant increase in the need
for jaundice treatment was noted for pre-term
babies in the review.
MT: Is the evidence on this conclusive?
TEL: Unfortunately, the clinical benefit from
routine use of delayed cord clamping in all
term deliveries is still unproven by high qual-
ity data. As such, the American College of
Obstetrics and Gynecology (ACOG) recom-
mends that the decision should be individu-
alized in low-risk term babies.
In pre-term infants, the ACOG opines that
the significant reduction of IVH associated
with delayed cord clamping is sufficiently
compelling to adopt this intervention.
The findings of a randomized controlled
trial conducted in Sweden suggest that babies
who experienced delayed cord clamping had
higher iron stores 4 months after birth. These
babies were also found to be less anemic [BMJ
2011;343:d7157]. Based on this and on earlier
research, the Royal College of Obstetricians
& Gynaecologists (RCOG) recommends that
the cord should not be clamped earlier than
is necessary based on a clinical assessment of
the situation.
The RCOG recognizes that the impact on
other substantive outcomes for the woman
and the infant remains unclear and suggests
that large randomized trials comparing the ef-
fects of alternative strategies for cord clamp-
ing are needed, with assessment of substan-
tive outcomes and long-term follow-up for
both mother and baby.
MT: When is delayed cord clamping not ap-
propriate?
TEL: Delayed cord clamping should not be
practiced if there are complications from de-
livery, such as severe maternal bleeding im-
mediately after delivery, if the umbilical cord
is wound tightly around the neck of the baby,
or if the baby is asphyxiated and requires im-
mediate resuscitation.
MT: Is it true that for the mother, delayed
clamping can prevent complications with
delivering the placenta?
TEL: It is postulated that by allowing the
placenta to drain of blood with delayed cord
clamping, placental separation may be en-
couraged, resulting in a shorter duration
needed to deliver the placenta. However,
clear maternal benefits have yet to be dem-
onstrated in the context of large randomized
controlled trials.
32 November 2013 Feature
MT: What are standard alternatives for the
procedure?
TEL: No “standard” alternative for delayed
cord clamping exists. The timing of when
to clamp the cord even when delayed cord
clamping is practiced remains controversial.
Some have suggested that waiting until the
absence of pulsations in the umbilical cord
might be appropriate.
A proposed alternative to delayed cord
clamping involves “milking the cord” so that
blood is encouraged to flow back to the baby.
A randomized trial has suggested that milk-
ing the cord four times was equivalent to de-
lay cord clamping for 30 seconds. However,
larger studies are needed to evaluate the risks
and benefits of this practice. Milking the cord
should be avoided if cord blood collection is
planned.
MT: When, if ever, is there a medical need
for parents to opt for delayed cord clamp-
ing?
TEL: Pre-term infants who have to be deliv-
ered for either maternal or fetal reasons may
benefit from delayed cord clamping. In term,
low-risk babies, the practice should be indi-
vidualized as recommended by the ACOG.
Potentially, term babies at risk for anemia or
whose mothers may be iron-deficient may
benefit from delayed cord clamping.
MT: How widespread is the practice in Sin-
gapore/your hospital(s)?
TEL: As the benefits of delayed cord clamp-
ing are not extensively studied, the practice
is uncommon although many obstetricians
will perform this at the patient’s request in
uncomplicated cases.
MT: Is delayed clamping safe for babies
born to mothers with blood-borne viruses,
given that immediate clamping minimizes
risk of transmission to the baby?
TEL: There is probably little data on this.
However, the National Institute of Health
in the US suggests that for HIV-infected pa-
tients, even though HIV-specific data on the
practice is lacking, there is no reason to mod-
ify the practice of delayed cord clamping in
HIV-infected mothers.
MT: What are the risks of delayed cord
clamping, if any, to the mother?
TEL: There should very little risk to the moth-
er when delayed cord clamping is practiced
in the absence of any other complications of
delivery. However, if the mother is bleed-
ing excessively and is in immediate need of
resuscitation, or if delaying cord clamping
may hinder the treatment of the mother in an
emergency situation, it would be preferable
not to delay clamping of the cord.
MT: Would you recommend it to your pa-
tients?
TEL: I would recommend it to mothers who
undergo an uncomplicated delivery of a term
pregnancy but provided they understand
that the baby may require phototherapy for
jaundice. I would recommend delayed cord
clamping in cases of preterm infants who un-
dergo uncomplicated deliveries without re-
quiring immediate resuscitation.
33 November 2013 In Practice
Weight management strategies in
primary care
Dr. Kevin Teh
Medical Director, Singapore Lipo, Body and Face,
a subsidiary of the Singapore Medical Group,
Singapore
O
besity and being overweight is defin-
itively linked to chronic diseases like
cardiovascular disease and diabetes
mellitus. It can shorten a patient’s life and
adds a heavy disease burden on the country’s
health system as a whole.
Current trends
While being underweight is not very com-
mon in modern society, being overweight is
increasing in numbers. In 1992, the prevalence
of obesity (defined by the WHO as BMI>30) in
Singapore was 5.1 percent. In 2004, it was 6.9
percent, and by 2010, incidence of obesity had
risen to 10.8 percent. The numbers for simply
being overweight (BMI > 25) has increased
from 21.1 percent in 1992, to 25.6 percent in
2004. Up to a third of Singaporeans could cur-
rently benefit from losing weight.
‘‘ Primary care physicians are vital
in highlighting the negative
effects of weight in a targeted
and timely manner.
Role of primary care in weight management
Primary care physicians are vital in high-
lighting the negative effects of weight in a
targeted and timely manner. Patients often ig-
nore their weight issues, as it is common to be
overweight or even obese.
Doctors should advocate patient awareness
of the real danger of metabolic syndrome.
After patients have passed the ‘pre-contem-
plation’ stage, doctors can give concrete tips,
dietary and exercise advice and pharmaco-
logical assistance. As our patients continue on
their journey, we can be the ones to motivate
and stop them from giving up.
Identifying candidates for weight manage-
ment strategies
A patient who has either an aesthetic or
physical trigger should engage in weight
management strategies. Patient may realize
that their clothes don’t fit anymore or people
around them have started commented on their
weight. They don’t feel good about themselves
and are increasingly self-conscious. The other
trigger is a life event such as having a mild
ischemic cardiac event or a transient ischemic
attack that makes the patient suddenly realize
that they need to take action.
GPs should look out for patients with a
BMI of over 27.5, especially those who have
an inability to lose weight despite being on a
treatment program. A motivated person can
usually lose 5-10 percent of his or her body-
weight over 6-12 months. If they cannot do so,
they should be assisted psychologically and
pharmacologically.
Those who have family risks of cardiovas-
cular or diabetes mellitus should be given
prompt help to thwart early onset of disease.
Doctors should ask the patient if they have
34 November 2013 In Practice
sleep apnea, osteoarthritis or a history of
smoking and check for hypertension, hyper-
lipidemia and impaired glucose tolerance.
Doctors should evaluate for medical condi-
tions that contribute to weight gain like hy-
pothyroidism, polycystic ovarian syndrome,
corticosteroid use and altered mental status
(eg, depression, anxiety, neuroses). Weight
gain can also be caused by secondary effects
of medications such as insulin, risperidone,
olanzepine, clozapine, valproate and gaba-
pentin. Occasionally, weight gain is due to an
undetected pregnancy.

Treating weight problems

A multidisciplinary approach to weight
management is important and should com-
bine dietary change, physical activity and be-
havioral modification. Dietary modification is
the simplest and most important component
of this in the initial phases of weight loss, but
often the hardest to implement.
A lowered caloric intake is the basis for
weight loss and a sustained reduction of No matter what diet modification is work-
1,000 kcal per day could result in a reduc- ing for your patients, always continue to
tion in bodyweight of 1kg per week. Sustain- guide them to enhance levels of fiber in their
ing a lowered caloric intake is not very easy, diet, as well as supplement vitamins and min-
however, even in the most motivated patient. erals for them.
Someone’s eating and sleeping habits must be Pharmacological assistance with appe-
analysed carefully for dietary modification to tite suppressants (such as phentermine) and
work. The best diet is the one that works for high quality natural supplements are useful
the individual patient. to augment the doctor’s armamentarium to
combat obesity.

‘‘ Someone’s eating and Finally, for sustainable weight loss, ensure

sleeping habits must
be analysed carefully for
dietary modification
to work
patients start on light to moderate exercise.
Anything is fine. Just get them moving! Cur-
rent Singapore health guidelines recommend
3 hours of physical activity per week. This
can be broken up throughout the week. For
example, a patient can engage in three exer-
cise sessions each week of 1 hour each. Find
35 November 2013 In Practice
something the patient enjoys and recommend
they keep the intensity level light to moder-
ate. Advise patients that training hard is not
smart when it comes to weight loss.
Psychological tips and neurolinguistic pro-
grams may also be effective to ‘train the mind’
and to avoid triggers. Creating the right en-
vironment for weight loss at home is a social
tool to make the weight loss sustainable. Pa-
tients can enlist their spouses and children to
motivate them by eating and dieting togeth-
er and avoid situations that encourage un-
healthy eating habits.
Specialist referral
If patients have comorbidities that need
specialist treatment (eg, hypothyroidism for
investigation, ischemic heart disease), they
should be co-managed with the appropri-
ate specialist. If they are morbidly obese
(BMI>35) and have failed repeated attempts
to control their diet and lifestyle, they may be
candidates for bariatric surgery.
GP challenges to patient weight management
The main challenge is that weight man-
agement and behavior modification takes a
lot of time and effort. This kind of time is of-
ten not available to a busy GP whose practice
is not primarily related to weight manage-
ment. A GP may also need the help of nutri-
tionists, dieticians, exercise trainers (and so
on) to truly have an ecosystem for success. A
complete and holistic solution is the best for
a patient, but is something not always read-
ily available.
 Journal of Paediatrics, Obstetrics & Gynaecology

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 37 November 2013 Calendar
NOVEMBER
2013 International Conference on Diabetes and 8th World Congress on Developmental Origins of
Metabolism/Asian Association for the Study of Health and Disease (DOHaD 2013)
Diabetes 17/11/2013 to 20/11/2013
6/11/2013 to 9/11/2013 Location: Singapore
Location: Seoul, Korea Info: DOHaD 2013 Congress Secretariat
Info: Korean Diabetes Association Tel: (65) 6411 6692
Tel: (82) 2-714-9064 Fax: (65) 6496 5599
Fax : (82) 2-714-9084 Email: secretariat@dohad2013.org
E-Mail: diabetes@kams.or.kr Website: www.dohad2013.org
Website: http://icdm2013.diabetes.or.kr/

9th International Symposium on Respiratory DECEMBER

Diseases
8/11/2013 to 10/11/2013 International Diabetes Federation (IDF)
Location: Shanghai, China World Diabetes Congress
Info: MIMS, China 2/12/2013 to 6/12/2013
Email: secretariat@isrd.org Location: Melbourne, Australia
Website: www.isrd.org Info: IDF
Tel: (32) 2 543 1631
18th Congress of the Asia Pacific Society of Fax : (32) 2 403 0830
Respirology (APSR) E-Mail: wdc@idf.org
11/11/2013 to 14/11/2013 Website: www.idf.org/worlddiabetescongress
Location: Yokohama, Japan
Info: Congress Secretariat American Society of Hematology (ASH)
Tel: (81) 3 5805 5261 Annual Meeting
Fax : (81) 3 3815 2028 7/12/2013 to 10/12/2013
E-Mail: info@apsr2013.jp Location: New Orleans, Louisiana, US
Website: www.apsr2013.jp/ Info: ASH
Tel: (1) 202 776 0544
17th Congress of the ASEAN Federation of Fax : (1) 202 776 0545
Endocrine Societies (AFES) Website: www.hematology.org
13/11/2013 to 16/11/2013
Location: Jakarta, Indonesia San Antonio Breast Cancer Symposium
Info: AFES Secretariat (SABCS) 2013
Tel: (62) 21 390 7703, 310 0075 10/12/2013 to 14/12/2013
Fax: (62) 21 392 8658,392 8659 Location: San Antonio, Texas, US
E-Mail: afes2013@gmail.com Info: Rich Markow, Director, Symposia
Website: www.afes2013.org Tel: (1) 210 450 1550
Fax : (1) 210 450 1560
American Heart Association (AHA) Scientific E-Mail: sabcs@uthscsa.edu
Sessions 2013 Website: www.sabcs.org
16/11/2013 to 20/11/2013
Location: Dallas, Texas, US International Conference on Obstetrics and
Info: AHA National Center Gynaecology (ICOG) 2013
Tel: (1) 214 570 5935 or (1) 888 242 2453 24/12/2013 to 25/12/2013
Fax : (1) 214 706 5262 Location: Bangkok, Thailand
E-Mail: sessions@heart.org Info: WASET
Website: www.myamericanheart.org Tel: (1) 971 559 099 620
Website: www.waset.org/conference/2013/12/bangkok/icog
 38 November 2013 Calendar
UPCOMING
10th Asian Pacific Congress of Hypertension
(APCH)
12/2/2014 to 15/2/2014
Location: Cebu, Philippines
Info: APCH Secretariat
Tel: (66) 2 748 7881
Fax : (66) 2 748 7880
E-Mail: apch2014@kenes.com
Website: www.apch2014.org

3rd Global Congress for Consensus in Pediatrics

& Child Health (CIP)
13/2/2014 to 16/2/2014
Location: Bangkok, Thailand
Info: Paragon Group
Tel: (41) 22 533 0948
Fax : (41) 22 580 2953
E-Mail: cip@cipediatrics.org
Website: www.cipediatrics.org

19th World Congress on Controversies in

Obstetrics, Gynecology & Infertility (COGI)
20/2/2014 to 23/2/2014
Location: Macau, China
Info: COGI Secretariat
Tel: (972) 73 706 6950
Fax: (972) 3 725 6266
E-Mail: cogi@congressmed.com
Website: www.congressmed.com/cogimacau

5th Congress of Asia Pacific Pediatric Cardiac

Society (APPCS)
6/3/2014 to 9/3/2014
Location: New Delhi, India
Info: APPCS Secretariat
Tel: (91) 11 2658 8116
Fax: (91) 11 2658 8663
E-Mail: appcs2014@gmail.com
Website: www.appcs2014.org

Asian Pacific Association for the Study of the

Liver (APASL) 2014
12/3/2014 to 15/3/2014
Location: Brisbane, Australia
Info: Gastroenterology Society of Australia
Tel: (61) 3 9001 0279
Fax : (61) 3 9802 8533
E-Mail: gesa@gesa.org.au
Website: www.apasl2014.com
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40 November 2013 After Hours

Peaceful Koya is a perfect hideaway from Japan’s busy

metropolises. Alexandra Kirsten followed the pilgrimage path
to Koyasan and spent a night in a Buddhist monastery.

T
hinking of Japan, most people would associate the country
with its big cities. But if you need a little meditative break
from the tourist filled streets in Kyoto or the overcrowded
shopping malls in Osaka, then take a train to the splendid highland
valley Koya, or Koyasan as it’s called in Japanese. Only about 1 and
a half hours away from Kyoto and Osaka, Koyasan is a totally dif-
ferent world.
Located in an 800-meter high mountain valley amidst the eight
peaks of the surrounding mountains lies Koyasan, a center of Bud-
dhist study and practice. About 12 centuries ago it was founded by
Buddhist monk Kobo Daishi Kukai, who was reminded by the land-
scape of a lotus flower surrounded by eight petals. His wish was to
41 November 2013 After Hours
establish a sanctuary deep in the mountains
where monks could practice and pray for
peace. The original monastery has now grown
into the town of Koya, including 120 temples
and a university dedicated to religious studies.
Koyasan might first remind you of a ski re-
sort. From the train station a cable car takes
you up the mountain where buses will bring
you to the town of Koya. As soon as you leave
the main roads behind, the scenery changes:
nestled in cherry and maple trees you will see
lots of small monasteries offering lodging to
pilgrims and tourists. Even if you are not a re-
ligious person, a night in a monastery is an
adventure. The friendly monks (most of them
speak a little English) will take you to your
traditional Japanese room with paper walls.
Simple but beautiful, it contains a tatami mat
for sleeping, a lavatory, a little Buddhist al-
tar and – the 21st century has arrived also in
Koyasan – a flat screen TV.
If you are willing to get up early, you are
invited to join the morning ceremony which
starts at 6 am. In the breaking dawn you can
listen to the prayers and songs of the monks.
After the ceremony a vegan breakfast con-
taining miso soup, rice and pickles is served
for the hungry guests. If sour pickled radish
is not really your preferred breakfast, you can
also visit one of the many little Japanese sweet
stores along the main road.
In 2004, the UNESCO designated Koyasan
as World Heritage Site for its cultural impor-
tance. One of the most important sites to see
in Koyasan is the Okunoin cemetery. The im-
mense graveyard lies in the middle of a for-
est and is the biggest in Japan. Besides the
many gravestones and memorials it contains
the mausoleum of Kobo Daishi Kukai. From
around the end of the 10th century, people
started to believe that Kukai had not passed
away, but entered an eternal meditation at
Okunoin. The faith in Kobo Daishi Kukai mo-
tivates still today lots of pilgrims to walk the
24-kilometer long path from Kudoyama to
Koyasan.
Following the stone markers of the last
part of the pilgrimage route through Koyas-
an, you will reach its endpoint, the Danjo Ga-
ran. The name Garan is derived from Sanskrit
and means “a quiet and secluded place where
monks may train.” Built in the 9th century, the
Great Pagoda, the Daito, was planned by Ku-
kai as the center of his monastic complex. The
Golden Hall, or Kondo in Japanese, is where
major Buddhist services are held. Originally
constructed in 819, it has been destroyed by
fire many times. Enshrined in the Kondo is
Bhaishajyaguru, the Medicine Buddha.
With its many temples, Koyasan offers
enough to see for days. If you feel finally re-
laxed after the peacefulness of Koyasan or
need a bed after a slightly hard night on a
tatami mat, you can easily take back the di-
rect train to Shin-Osaka and indulge yourself
with some hot handmade udon noodles.
42 November 2013 Humor

“You seem to be in good health.

An early sign that eventually
“I’m sorry Mr. Schaaffhausen, but your insurance doesn’t cover razor cuts!” you’re going to be sick!”

“It’s too bad you’re having

kidney surgery, I’m much
“Let’s go back to your childhood!” better with the liver!”

“No wonder he was screaming

“Just keep an eye on it and call “Look Doctor ... Mr. Perlmutter with pain. Kidney stones this
me in case it gets any bigger!” is showing off again!” size can make you rather
uncomfortable!”
PRINT • ONLINE • DIGITAL EDITION
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JAN/FEB 2012
NOV/DEC 2012Vol.
Vol.38
38No.
No.16 Your partner in paediatric
and O&G practice
JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

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OBSTETRICS

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Functions and Basics
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CME ARTICLE

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Bleeding

NOV/DEC 2012 Vol. 38 No. 6 Your partner in paediatric

and O&G practice

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