JUNE 2014

Asian asthmatics underestimate

seriousness of their condition
CONFERENCE
Football to help
end malnutrition,
obesity in children
NEWS
Hyperuricemia
increases fracture
risk in older men
RESEARCH
REVIEWS
Edible mushrooms
may reduce the risk
of breast cancer
FORUM
Drug policy in Asia
is diabolical
JUNE 2014 2
Asian asthmatics underestimate
seriousness of their condition
CHUAH SU PING
A
newly published survey has revealed a wor-
rying void between what patients believe is
adequate control of their asthma and what they
can actually achieve.
The multi-country REcognise Asthma and
Link to Symptoms and Experience (REALI-
SE
TM
) Asia survey reported that 89 percent of
the 2,467 asthma patients included in the study
believed that their asthma was well controlled.
However, according to the GINA* guidelines,
only 18 percent had their asthma under control.
Across the region, patients consistently un-
derestimate the seriousness of their asthma.
They are less likely to pay attention to symp-
toms when they are not severe, which has pro-
found effects on their daily lives, including work
and school performance, said Dr. Tan Tze Lee,
adjunct assistant professor at the National Uni-
versity of Singapore and a member of the RE-
ALISE
TM
Asia Steering Committee.
According to the survey, 82 percent of pa-
tients believed that their asthma was not seri-
ous; however, 73 percent experienced health
problems directly related to asthma. In fact, 71
percent reported having interrupted sleep due
to asthma symptoms at least one night each
week, and more than one-third have required
emergency hospital treatment for their asthma
in the past year. The findings also confirm the
continued high burden of the disease with
more than 92 percent still experiencing a range
of major symptoms such as coughing, breath-
lessness and chest tightness.
The importance of addressing
patient attitudes
Of particular concern, 41 percent of respon-
dents did not see the need to take their medi-
cation regularly as they did not experience any
incapacitating symptoms or asthma attacks.
Nearly half deemed their inhaler use a nuisance
and only 14 percent took their asthma medica-
tion daily, as prescribed. Additionally, 72 percent
believed they were able to manage their asthma
without the help of a doctor.
Patients could be managing their condition
better, which would positively impact their qual-
ity of life. It is important that they speak with their
doctor about improving the control of their asth-
ma, said Tan. He added that the REALISE
TM
Asia
study revealed that patient attitudes about asth-
A large survey of more than 2,000 Asian patients with
asthma revealed a gap between perception and reality in
terms of how well their symptoms were controlled.
JUNE 2014 3
ma have a real and harmful effect on their health
and quality of life. Patients who believe they have
their asthma under control will likely forego medi-
cations that would prevent severe asthma attacks
from happening. Only by addressing patients at-
titudes about their condition can we create a tar-
geted approach to improve asthma management
and lower the burden of the disease in Asia.
The REALISE
TM
Asia survey involved 2,467
patients with asthma aged 18 to 50 in eight
Asian countries and aimed to assess patient
attitudes and behaviors towards their disease.
Sponsored by Mundipharma Pharmaceuticals,
the study was conducted in partnership with
a steering committee of respiratory experts
across the region.
*Global Initiative for Asthma
READ JPOG ANYTIME, ANYWHERE.
Download the digital edition today at www.jpog.com
JUNE 2014 4
Sleep deprivation a growing problem
PANK JIT SIN
P
eople are becoming increasingly sleep de-
prived and this can result in serious conse-
quences, warns a US expert.
Speaking at a media interview in conjunc-
tion with the 12th International Congress on
Obesity, Dr. Teofilo Lee-Chiong, a professor of
medicine at the University of Colorado Denver
School of Medicine, said sufficient sleep is im-
portant for growth and restoration; metabolic
and energy balance; immune function; brain
development; and learning.
Many people under-appreciate the impor-
tance of sleep. This is especially evident in
the modern world, with its 24-hour connectivity.
Teofilo noted that over the last 40 years, nightly
sleep duration has decreased by an average of
1 to 2 hours, and that one-third of young adults
sleep less than 6 to 7 hours every night.
While sleep deprivation has many causes
shift work, late night television shows, side
effects of coffee and tea sleep and medical
disorders play an important role in sleep depri-
vation, with the most common being obstructive
sleep apnea (OSA).
OSA is estimated to affect one in six middle-
aged men and up to one in 10 women. The
condition is more prevalent in those with co-
morbidities such as diabetes mellitus, asthma
and stroke. Based on these estimates, almost
three million Malaysians could have sleep ap-
nea, with many still undiagnosed.
The lay person may not be aware that many
diseases can be linked to OSA, including hy-
pertension, heart failure, arrhythmia, stroke,
depression, memory loss and learning impair-
ment, said Teofilo. In light of this, it is important
that OSA is diagnosed and treated.
In the GP setting, patients with straightfor-
ward OSA can be effectively managed by those
with adequate knowledge of the disorder. Prop-
erly trained GPs can initiate screening, conduct
clinical history, perform the necessary examina-
tions and testing, prescribe treatments (including
proper sleep hygiene, maintenance of optimal
weight and positive airway pressure therapy) and
monitor responses to therapy, said Teofilo.
Referral to a sleep specialist (including sleep
physicians, surgeons and dentists) should be
considered in patients with complicated medical
histories, who have major medical comorbidities
OSA is estimated to affect up to 1 in 6 middle-aged men
and 1 in 10 women.
JUNE 2014 5
or who have failed to respond to positive airway
pressure therapy.
Sleep deprivation consequences
Some of the worlds most devastating ac-
cidents have been associated with inade-
quate sleep, noted Teofilo. For instance, the
Chernobyl nuclear accident, Exxon Valdez oil
tanker accident and the space shuttle Chal-
lenger explosion were all attributable to sleep
deprivation. [Sleep, Performance and Public
Safety. Available at: http://healthysleep.med.
harvard.edu/healthy/matters/consequences/sleep-
performance-and-public-safety Accessed on 1
April]
Sleep deprivation is associated with up to 10
percent of motor vehicle crashes and over 50
percent of work-related accidents, while about
20 percent of pilots admit to making serious er-
rors due to sleepiness.
In order to improve the situation, Teofilo
called for improved visibility of the problem
related to sleep deprivation and to affirm soci-
etys role to protect sleep.
MT-thru-MIMS_0314-2.pdf 1 6/18/14 2:40 PM
JUNE 2014 FORUM 7
Drug policy in Asia is diabolical
Its time to treat drug addiction
as a health issue
D
rug policy all over the world is undergoing
metamorphosis. After decades of incar-
ceration, judicial corporal punishment, and the
death penalty for drugs, governments are realiz-
ing that drug addiction is primarily a health and
welfare issue. Guided by scientific evidence,
they are increasingly aware that punitive sanc-
tions and search and arrest procedures do not
reduce drug use. Rather, they increase crime,
increase HIV, hepatitis C, and other blood borne
diseases, and target racial minorities. All of
these result in a vicious cycle of inequality and
poverty. Entire populations of productive young
men and women have had their lives wiped out
because of criminal records for small amounts
of drugs, devastating stigma, and, as a result of
the marginalization, increased risk of disease.
I have just returned from the International So-
ciety for the Study of Drug Policy (ISSDP) con-
ference in Rome, which is one such forum for
the exchange of the latest research on drugs
and drug policy.
Contrary to what a layperson might think, this
is not a conference where people advocate drug
use. Based on the findings of a qualitative study
of 26 adult drug users in the UK, Dr. Rebecca
Askew, Lecturer in Criminal Justice, School of
Law, Liverpool John Moores University, reported
that drug users thought that drug use should be
tolerated, but not advocated.
In the ISSDP, one finds a convergence of
economists, physicians, lawyers, epidemiolo-
gists, criminologists, behavioral scientists and
social scientists presenting the most recent
research on what works and what doesnt. I al-
ways love this conference because all the bril-
Fifa Rahman (LLB, Law, MHL, Health Law), Policy Manager, Malaysian AIDS Council,
reports back from the International Society for the Study of Drug Policy (ISSDP) 2014
held recently in Rome, Italy, and shares her views about the alarming discrepancy
between international best practices for the treatment of people with drug addiction
and drug policy implemented in the Asia region.
Across Asia, people with drug addiction are being jailed,
humiliated, tortured.
JUNE 2014 FORUM 8
liant minds in the room inspire me, feeding me
with information that I will use in my work.
Of course Im drafting this with Asia in mind.
All across Asia, people are jailed, humiliated,
and forced into compulsory detention (reha-
bilitation), where a bunch of military men make
them wake up early and march all day, ignoring
the possibility that many detainees may have
been functional drug users who took a pill on
the weekends and went to their office job during
the week. This kind of treatment also ignores
a health care reality that the brains of many
people who use drugs have been changed by
addiction forever.
In Malaysia and Indonesia, people are jailed
for personal possession of cannabis, a drug
which is far less harmful than alcohol.
We should remember that if President Obama
had been jailed for cannabis use, well, he
wouldnt be President Obama. He may well have
graduated to harder drugs in jail, made relation-
ships with fellow inmates, struggled to find a job
post-release, and ended up collecting crushed
cans and selling them to junk dealers to survive.
How many of these Obamas are out there then?
And more pertinent, how many Obamas are
suffering right now in jails across Asia, awaiting
death sentences, awaiting their buttocks being
ripped apart by judicial whipping?
I know what you are thinking. This is a bleak
story and its never going to change in Asia. Be-
sides, drug users dont want to change.
Dr. Tim Rhodes, professor at the London
School of Medicine and Tropical Hygiene, qual-
itative research guru, said that during a study
he was involved with in Kenya (presented at
ISSDP), a female drug user living with HIV said:
This is not the life I asked God for. This is not
the life I went to school for.
At a drug law reform roundtable held at the
Malaysian Parliament on 3 December 2013, Man-
ja Marsyad, a female former drug user currently
on methadone maintenance therapy told a room
full of government officials and politicians: There
was not a single day that I didnt want to change.
So its not an issue of drug users being an-
ti-health, because they obviously arent. This
is about governments being anti-health for the
sake of rhetoric, in spite of plenty of evidence on
pro-health measures.
Southeast Asian governments would do well
to review the ASEAN Drug-Free by 2015 strat-
egy. This lofty aspiration, while undoubtedly
born from altruistic motives, serves no purpose
but to reinforce and support harsh punishments.
Deborah Alimi, PhD candidate from Universite
Paris I Pantheon Sorbonne presented at ISSDP
that with the 2016 UN General Assembly Special
Session coming up, it is high time that govern-
ments mitigate the risk to future development.
Increasing social expenditure and refocusing
away from criminalization must occur. Professor
Alex Stevens, Criminology, University of Kent, pre-
sented at ISSDP that high social expenditure is a
sufficient condition for low injecting drug use.
Statistics coming out of Malaysia show that
voluntary methadone treatment has reduced il-
licit heroin use to around 4 percent as compared
to before treatment, and that 75.9 percent of cli-
ents enrolled were not rearrested for any crime.
Asian governments must act on science, and
they must act now.
JUNE 2014 NEWS 9
Hyperuricemia increases fracture risk
in older men
ELVIRA MANZANO
H
igh serum uric acid levels (hyperuricemia)
are associated with an increased risk of hip
fractures in older men, research has shown.
In an analysis of data from 4,692 patients
who had participated in the Cardiovascular
Health Study, older men (age 65 years) with
higher uric acid levels (7 mg/dL) were 62 per-
cent more likely to fracture a hip than those with
lower levels (hazard ratio [HR] 1.62, 95% CI,
1.075-2.449; p=0.02) in a fully adjusted model.
No such association was found in women. [Na-
tional Kidney Foundation 2014 Spring Clinical
Meeting; Abstract 409]
Of the 1,963 men assessed, 430 had uric
levels of 7 mg/dL or higher. These men were
more likely to be obese, had higher levels of
insulin, C-reactive protein and cystatin C, and
were on diuretics. During 11 years of follow-up,
156 first-incident fractures occurred.
Lead researcher Dr. Tapan Mehta from the
University of Colorado, Denver, said one pos-
sible mechanism that might explain the link
between increased serum uric acid and hip
fractures is that high uric acid levels impair ni-
tric oxide availability in the bone. Uric acid may
also induce bone inflammation and suppress
vitamin D activation, which can increase bone
fragility and fracture risk.
High serum urate level is produced during
breakdown of purine, which is found in many
foods, particularly in meat and seafood. Previ-
ous studies have also linked high serum uric
acid to renal disease progression and meta-
bolic syndrome with or without a low estimated
glomelular filtration rate (eGFR). [J Rheumatol
2014;41:955-962; J Rheumatol 2009;36:1691-
1698]
Mehta said more research is needed to es-
tablish the link between high urate levels and
increased fracture risk.
Commenting on the study, Dr. Siow Hua
Ming, consultant orthopaedic surgeon at Provi-
dence Orthopaedics, Mount Elizabeth Novena
Specialist Centre, Singapore, said while the
results are interesting, further studies are war-
ranted to see if there is an across-the-board
increase in fracture risk among patients with
high serum uric levels. The results may also
be confounded by other factors such as gout in
people who are not practicing healthy lifestyle,
he added.
Older men with high uric acid levels may be at higher risk
of hip fracture.
JUNE 2014 NEWS 10
Tight glycemic control prolongs
survival in diabetes
ELVIRA MANZANO
I
ntensive glycemic control with insulin pro-
vided better long-term survival compared with
standard glucose management in an extended
follow-up of diabetic patients who had a heart
attack.
The prospective, randomized, open-label DI-
GAMI-1* trial showed that patients who received
intensive insulin treatment after an acute myo-
cardial infarction (MI) lived 2.3 years longer than
those treated with standard care (median sur-
vival time, 7 years vs 4.7 years p=0.027). The
survival advantage of intensified insulin therapy
persisted for up to 8 years after randomization.
[Lancet Diabetes Endocrinol 2014; doi:10.1016/
S2213-8587(14)70088-9]
Intensified insulin-based glycemic control
after acute myocardial infarction in patients
with diabetes or hyperglycemia at admission
had a long-lasting effect on longevity, said
lead author Dr. Viveca Ritsinger from the Kar-
olinska Institute in Stockholm, Sweden, and
colleagues.
Although the effect of glucose lowering
might be less apparent with currently available,
more effective lipid- and blood-lowering drugs,
improved glycemic control might still be impor-
tant for longevity after acute MI, the research-
ers said.
DIGAMI-1 was conducted in 19 hospitals in
Sweden between 1990 and 1993. The study
included 620 patients who had an acute MI in
the last 24 hours, with blood glucose concentra-
tions of >11mmol/L, randomized to receive in-
tensive insulin therapy (intravenous infusion for
24 hours, followed by injections four times daily
for 3 months) or standard glucose management
(insulin given only as required by attending
physician). The primary endpoint was mortality
in both the original study and follow-up. Three-
year results had been reported earlier.
At 7.3 years, 89 percent of patients in the in-
sulin-treated group and 91 percent in the control
group had died.
Ritsinger said patients with a low cardiovascu-
lar risk appeared to benefit most from intensive
glycemic control. However, in those with long-
standing diabetes and more advanced cardio-
vascular disease it did not seem to improve mor-
tality.
In an accompanying editorial, Dr. Denise
E. Bonds from the National Heart Lung and
Blood Institute, National Institutes of Health
in Bethesda, Maryland, US said the DIGAMI-1
trial reinforced the importance of tight glucose
control even when other risk factors such as
lipid or blood pressure cannot be or are not
modified. Second, and perhaps most im-
portantly, it provides an important reminder
of how quickly medicine is advancing... In 20
years, we have gone from few glucose-lower-
ing therapies to over half a dozen oral therapy
drugs, plus insulin, plus effective treatments
JUNE 2014 NEWS 11
to reduce the risk of elevated lipids and blood
pressure.
Now, the challenge is how to choose the
best treatment option for our patients, she
added.
*DIGAMI 1: First Diabetes Mellitus Insulin Glucose Infusion in
Acute Myocardial Infarction
Two meals better than six for some
diabetics
ELVIRA MANZANO
E
ating two large meals a day may be more
beneficial than six small, frequent meals
with the same caloric content for weight loss
and glucose control in patients with type 2 dia-
betes (T2D), a randomized crossover study has
shown.
Researchers compared the effect of two
low-energy diet regimens two large meals
(breakfast and lunch) versus six small meals
(breakfast, dinner, lunch and three snacks in
between) on body weight, hepatic fat content
(HFC), insulin resistance and beta-cell function
in diabetic patients (age, 30 to 70 years), with
body mass index (BMI) of 27 to 50 kg/m
2
and
an HbA1c level of 6 to 11.8 percent. One group
received two large meals, the other group six
small meals a day for 12 weeks. Both diets have
low caloric content (less than 500kcal of recom-
mended daily intake). All patients continued oral
hypoglycemic medications. After 12 weeks, the
regimens were switched. [Diabetologia 2014;
doi: 10.1007/s00125-014-3253-5]
At the end of the study period, both regimens
significantly reduced body weight, HFC, glucose
and C-peptide levels (p<0.001 for all). However,
greater reductions in all four parameters were
seen with the two-meal regimen.
Eating only breakfast and lunch also in-
creased insulin sensitivity greater than six meals
spread throughout the day. For T2D patients
on hypoenergetic diet, eating larger breakfasts
and lunches may be more beneficial than six
smaller meals during the day, said study author
Dr. Hana Kahleova from the Institute for Clinical
and Experimental Medicine in Prague, Czech
Republic, and colleagues.
The improvement in insulin sensitivity may
have positively influenced the reduction in blood
glucose and HFC, or conversely, the reduction
in HFC may have led to improvement in insu-
lin sensitivity, said the authors. Considering that
HFC is associated with insulin resistance inde-
pendent of BMI, T2D and metabolic syndrome,
the greater reduction in HFC with the two-meal
regimen is one of the most important results of
our study.
Glucagon levels also decreased with the two-
meal regimen, but increased with the six-meal
JUNE 2014 NEWS 12
regimen. This reduction is a very positive find-
ing because abnormally high levels of serum
glucagon influence dysregulated glucose pro-
duction in the kidney and abnormal glucose ho-
meostasis in T2D.
No adverse effects were observed for either
diet.
The findings contradict a commonly held be-
lief that eating smaller, more frequent meals is
actually healthier. Further studies are warranted
before recommendations regarding meal fre-
quency can be offered to diabetic patients, said
the authors. Novel therapeutic strategies should
incorporate not only energy and macronutrient
content, but also the frequency and timing of
meals.
E-cigarettes can be part of the solution,
not the problem, say scientists
GREG TOWN
O
ver 50 top scientists from 15 countries
recently appealed in a letter to the World
Health Organization (WHO) to reconsider its
stance on e-cigarettes, warning that the or-
ganization risks missing an opportunity to
markedly reduce morbidity and mortality as-
sociated with smoking.[http://nicotinepolicy.
net/n-s-p/1753-who-needs-to-see-ecigs-as-
part-of-a-solution]
The scientists were reacting to a leaked doc-
ument from a WHO-sponsored Framework Con-
vention on Tobacco Control (FCTC) preparatory
meeting indicating that the WHO considers e-
cigarettes a threat to public health and intends
to sideline their use as a possible alternative to
regular tobacco and cigarettes.
If the WHO gets its way and extinguishes e-
cigarettes, it will not only have passed up what
is clearly one of the biggest public health in-
novations of the last three decades that could
potentially save millions of lives, but it will have
abrogated its own responsibility under its own
charter to empower consumers to take control
of their own health, something which they are
already doing themselves in their millions, said
letter signatory Professor Gerry Stimson, emeri-
tus professor at the Imperial College in London,
UK. E-cigarettes are part of the solution, not the
problem.
While tobacco control policy efforts over the
past three decades have been linked with re-
ductions in smoking prevalence in some parts
of the world in mid to high income countries
smoking rates continue to increase in the de-
veloping world.
For the WHO to suggest that e-cigarettes are
as risky as other tobacco products would send
an erroneous and bleak message to the millions
of current e-cigarette users who have used them
to quit smoking, said letter signatory Professor
JUNE 2014 NEWS 13
Robert West, professor of health psychology
and director of tobacco studies at University
College in London, UK. It would discourage
smokers from trying them and we would miss
out on a major opportunity to reduce smoke re-
lated deaths globally.
In the letter to the WHO director-general Mar-
garet Chan, the 53 signatories argue that tobac-
co harm reduction products could play a signifi-
cant role in meeting the 2025 UN objectives to
reduce noncommunicable diseases.
Given the relative novelty of e-cigarettes, re-
lated regulations into their use, legislation, and
public health investigations are pending in many
countries. However, some Asian nations such as
Singapore and Cambodia have been quick to
ban the devices entirely.
In a combined statement to Medical Tribune,
Singapores Ministry of Health (MOH), Health
Promotion Board (HPB) and Health Sciences
Authority (HSA) said: We are concerned that
e-cigarettes can be a gateway to developing a
smoking habit, particularly among the young as
nicotine is addictive. To protect the public from
any potential health risks associated with e-cig-
arette consumption, the import... , distribution,
sale, or offer for sale of e-cigarettes is prohibited
in Singapore.
HPB-led tobacco control initiatives appear
to have had little impact on the prevalence of
smoking in Singapore over the last decade. The
most comprehensive survey data available sug-
gest the smoking rate in the country is trending
upwards from 2004 to 2010, the prevalence of
smokers in Singapore aged 18 to 29 increased
markedly, from 12.3 percent to 16.3 percent, a
rise of about 33 percent. [Singapore National
Health Survey 2010]
JUNE 2014 DRUG PROFILE 14
Pertuzumab for HER2-positive
metastatic breast cancer
Naomi Adam, MSc (Med),
Category 1, Accredited Education Provider (Royal Australian
College of General Practitioners)
Introduction
The past few decades have seen a steady im-
provement in prognosis and mortality rates for
breast cancer, particularly with the introduction
of specific, molecularly targeted agents. Notable
among these was trastuzumab an antibody di-
rected at human epidermal growth factor recep-
tor 2 (HER2). Around 15 to 20 percent of breast
cancers are HER2-positive, with overexpression
of the human epidermal growth factor receptor
2 oncogene (ERBB2, HER2, or neu). This re-
sults in elevated levels of HER2; a key signaling
molecule involved in pathways that promote cell
proliferation, migration and invasion. [Cancer
Treat Rev 2014;40:276-284, Clin Breast Cancer
2013;13:315-324]
Trastuzumab suppresses HER2 signaling by
binding to the extracellular domain of the protein.
It dramatically improves outcomes in HER2-pos-
itive disease and is now recommended as stan-
dard therapy for all patients with HER2-positive
breast cancer. Nevertheless, HER2-positive met-
astatic disease remains a particularly aggressive
form of breast cancer with a poor prognosis. This
has prompted the development of new treatment
strategies such as dual antibody therapy. [Clin
Breast Cancer 2010;10:489-491]
Pertuzumab
Mode of action
HER protein exists in four different forms:
HER1 (also known as EGFR), HER2, HER3 and
HER4. The formation of a dimer between two
HER molecules is a key step in the signaling
pathways under control of this system. These
paired molecules may be either homodimers
of the same form (eg, HER2:HER2) or heterodi-
mers comprising two different forms of HER pro-
tein. One limitation of trastuzumab is that it only
HER2-positive metastatic breast cancer is a highly aggressive form of the disease,
with a poor prognosis. This has prompted the development of novel dual targeted
therapies such as pertuzumab (Perjeta

, Roche), a recombinant humanized monoclonal

antibody, which we profle here.
JUNE 2014 DRUG PROFILE 15
prevents the formation of HER2:HER2 homodi-
mers: It does not prevent heterodimers, and this
is thought to represent an escape pathway by
which progression on trastuzumab therapy oc-
curs. Therefore, the prevention of HER2 dimer-
ization in combination with trastuzumab repre-
sents an important potential therapeutic strategy
for more comprehensive blockade of HER2-me-
diated disease progression. [Clin Breast Cancer
2010;10:489-491]
Pertuzumab a recombinant humanized
monoclonal antibody that targets the extracel-
lular dimerization domain (Subdomain II) of
HER2 is the first member of a new class of
anticancer therapy. It blocks ligand-dependent
heterodimerization of HER2 with other HER fam-
ily members and inhibits ligand-initiated intra-
cellular signaling through two major pathways
mitogen-activated protein (MAP) kinase, and
phosphoinositide 3-kinase (PI3K). Inhibition of
these pathways can result in cell growth arrest
and apoptosis, respectively. Pertuzumab also
mediates antibody-dependent cell-mediated
cytotoxicity. [Perjeta (pertuzumab) Prescribing
Information]
Clinical efficacy
The pivotal phase III registration study for per-
tuzumab was CLEOPATRA (CLinical Evaluation
Of Pertuzumab And TRAstuzumab). This investi-
gation enrolled 808 adults with a histologically or
cytologically confirmed diagnosis of HER2-over-
expressing adenocarcinoma of the breast with
locally recurrent or metastatic disease. Patients
may have received prior systemic breast cancer
treatment in the neoadjuvant or adjuvant set-
ting, but must have experienced remission for at
least 12 months before diagnosis of metastasis
in order to be eligible. Those with more than one
previous hormonal regimen, a cumulative dose
of doxorubicin > 360 mg/m
2
, an LVEF decline
to < 50 percent during previous trastuzumab
therapy, central nervous system metastases,
another malignancy, inadequate hematological
function or impaired liver or renal function were
excluded from the study. All subjects were given
trastuzumab (loading dose 8 mg/kg followed by
6 mg/kg every 3 weeks) and docetaxel (75 mg/
m
2
, increased to 100 mg/m
2
if tolerated). On this
background, patients were randomly assigned
to either pertuzumab (840 mg in cycle 1, then
420 mg every three weeks) or placebo. [Clin
Breast Cancer 2010;10:489-491]
The primary endpoint of CLEOPATRA was in-
dependently assessed progression-free survival
(ie, time from randomization to first documented
radiographic evidence of progressive disease or
death from any cause within 18 weeks after the
last independent assessment of tumors). It was
found that pertuzumab significantly prolonged
progression-free survival compared with pla-
cebo (12.4 months versus 18.5 months; hazard
ratio for progression or death, 0.62; p<0.001).
[N Eng J Med 2012;366:109-119] There was
also a significant increase in overall survival with
pertuzumab: at the time of data cut-off 38 per-
cent of patients in the placebo group had died
compared with 28 percent in the pertuzumab
group. Median overall survival was 37.6 months
with placebo, but had not yet been reached in
the active group (hazard ratio 066; p=00008).
[Lancet Oncol 2013;14:461-471]
JUNE 2014 DRUG PROFILE 16
An extensive program of completed and on-
going clinical trials is further revealing the role
of pertuzumab in HER2-positive breast cancer.
Enhanced progression-free survival has been
demonstrated in advanced breast cancer; in pa-
tients whose metastatic disease has progressed
despite prior treatment with trastuzumab and
up to three lines of prior chemotherapy, as well
as in patients who have not received any prior
chemotherapy or biological therapy. [Ann Oncol
2012;23:791-800] In the neoadjuvant setting, a
high rate of clinical response has been shown
in the phase II NeoSphere study [Lancet Oncol
2012;13:25-32] and early HER2-positive disease
is emerging as another area where pertuzumab
has the potential to enhance outcomes. Given
the anti-tumor activity seen in the metastatic
and the neoadjuvant setting, pertuzumab is now
also being studied in the adjuvant setting, used
in conjunction with chemotherapy plus trastu-
zumab in patients with operable HER2-positive
primary breast cancer. [Clin Breast Cancer
2010;10:489-491]
Adverse effects
Common adverse effects associated with
pertuzumab include diarrhea, nausea/vomiting,
asthenia and skin rash. In clinical trials, the inci-
dence of diarrhea ranged between 27 percent
and 72 percent. Severe diarrhea (grade 3/4)
occurred in just 37.9 percent; the majority of
cases were manageable (grade 1 or 2) and self-
limiting. Similarly, up to two-thirds of patients in
clinical trials experienced nausea/vomiting and/
or asthenia but less than 2.5 percent of cases
were of a severe grade (3/4). Skin rash with per-
tuzumab was also usually low grade and ap-
peared in the papulopustular (acneiform) phe-
notype, similar to that seen with other epidermal
growth factor receptor and HER2 targeting
agents. [Clin Breast Cancer 2010;10:489-491]
Because HER signaling plays a key role in the
maintenance of homeostasis in the cardiac myo-
cyte, there is a concern that pertuzumab may be
associated with cardiotoxicity. Reassuringly, a
recent meta-analysis found that there were rela-
tively low levels of asymptomatic left ventricular
systolic dysfunction or symptomatic heart failure
among patients treated with pertuzumab. There
was also no notable increase in cardiac adverse
effects when pertuzumab was given in combi-
nation with other anticancer agents (eg, trastu-
zumab). [Ann Oncol 2012;23:791-800] It is still
recommended however that cardiac risk factors
are taken into account when deciding whether
to use pertuzumab. [Perjeta (pertuzumab) Pre-
scribing Information]
Dose and administration
Pertuzumab must only be given as an intra-
venous infusion. The initial dose is 840 mg ad-
ministered over 60 minutes, followed every 3
weeks thereafter by 420 mg administered over
30 to 60 minutes. When used in the setting of
metastatic breast cancer pertuzumab is given in
combination with trastuzumab and docetaxel.
In the neoadjuvant setting pertuzumab is given
with trastuzumab and docetaxel pre-operatively
every 3 weeks for 3 to 6 cycles. [Perjeta (pertu-
zumab) Prescribing Information]
JUNE 2014 CONFERENCE COVERAGE 17
The 5 Ds of pediatric research
Philippine Pediatric Societys 51st Annual Convention, 7 to 9 April 2014,
Philippine International Convention Center, Manila
DR. JAMES SALISI
D
evelopmental issues, dependency, dif-
ferential epidemiology, demographic
patterns and dollars these are the 5 Ds that
set pediatric research apart from all other
researches, making it more difficult to do,
according to Dr. Michael D. Cabana, professor
of pediatrics, epidemiology and biostatistics at
the University of California in San Francisco.
The attainment of optimal, physical, men-
tal and social wellbeing of all infants, children,
adolescents and young adults is the goal of
pediatrics. Medical advances through research
make it possible to attain this goal. Research is
the systematic investigation designed to answer
a scientific question and aims to contribute to
general knowledge, the products of which be-
come useful to society.
However, not all researches are the same,
and pediatric research is not research on small-
er adults. This is where the developmental is-
sue comes in, said Cabana. Many adult dis-
eases have their roots in infancy and childhood.
These include heart disease, chronic obstruc-
tive pulmonary disease and allergic disease.
For example, the Muscatine Heart Study in Iowa,
USA showed that elevated levels of cholesterol,
blood pressure and body mass index in child-
hood predict elevated adult levels and meta-
bolic syndrome. Because of these observations,
the need to start investigating diseases in child-
hood arises.
Cabana further explained that children are
a vulnerable population and this highlights the
issue of dependency. Obtaining consent to in-
clude them in clinical trials is a complex matter.
Investigators need to ensure and show the insti-
tutional review board that the childrens rights
are protected throughout the study.
The epidemiology of diseases is unique in
children. Many rare diseases manifest in a very
small percentage of children and some diseas-
es are unique to them. This characteristic brings
to fore the differential epidemiology of diseases
in children.
Pediatric populations all over the world are
also extremely diverse, especially in the US
where there is a large of immigrant popula-
tion. According to Cabana, studies have to
Developmental issues, dependency, differential
epidemiology, demographic patterns and dollars
these are the 5 Ds that set pediatric research apart from
all other researches.
JUNE 2014 CONFERENCE COVERAGE 18
be culturally as well as developmentally ap-
propriate.
Lastly, the issue of return on investment or
dollars that is put into pediatric research, which
puts into question the value of investing into
pediatric care whose final product is realized
over an extended period of time. Proving the ef-
fectiveness and benefits of early intervention is
challenging.
How then can one promote the importance of
research to patients and their families? Cabana
suggested three simple action items: be aware
of ongoing research studies, be supportive of
parents and families who are participating in
studies, and refer patient who might be eligible
for studies.
JUNE 2014 CONFERENCE COVERAGE 19
Dealing with gender issues
in adolescents
DR. JAMES SALISI
F
ew things worry parents more than finding
out their children are gay. Stigma still per-
sists and much more so in cases when their chil-
dren exhibit non-conformist sexual behavior.
It is important that we bring up the develop-
ment of an individual so that he is able to become a
mature and well-functioning adult later on; that he
be able to achieve a mature level of sexuality. This
process entails a lot of experimentation, a lot of
exploration and a lot of these are actually normal,
said Dr. Erlinda Cuisia-Cruz, associate chief of
Adolescent Center, Philippine Childrens Medical
Center.
A healthy adolescent sexual development
means that he is able to have positive feelings
about body image, have the capacity to appro-
priately manage sexual arousal and desire, and
make responsible decisions about sexual be-
havior.
Gender refers to the attitudes, feelings and
behaviors that a given culture associates with
a persons biological sex, said Cuisia-Cruz. On
the other hand, gender identity, according to
the American Psychological Association, refers
to ones sense of oneself as male, female or
transgender.
Gender role may be defined as what society
expects a child to do because of his sex. This is
strongly influenced by upbringing and expecta-
tions, identification with the males and females
in his life, TV and sports heroes, and a childs
relationship with his parents.
However, gender expression or the way in
which a person acts to communicate gender
within a given culture, may or may not be con-
sistent with socially prescribed gender roles,
and may or may not reflect his gender identity,
noted Cuisia-Cruz.
When a child hits early adolescence stage,
issues of independence arise. He feels the need
to separate from the family as he becomes in-
creasingly involved with his or her peers. It is
also during this stage that a child begins to have
an interest in sex.
Discussion of sexuality with adolescents and
non-judgmental communications about sexual
orientation are widely recommended by profes-
sional societies especially when dealing with
Gender role may be defined as what society expects a
child to do because of his sex.
JUNE 2014 CONFERENCE COVERAGE 20
homosexual identity. Despite this, there is a
low rate of disclosure because of homophobia
among health care providers; lack of provider
training, knowledge and comfort about lesbian,
gay and bisexual issues; and the patients con-
cerns about confidentiality.
Pediatricians are encouraged to examine
their own reactions and biases before interact-
ing with their patients. If one is not comfortable
to give comprehensive assessment and man-
agement, one should refer to those who are.
The value of talking about sexual practices and
behavior in a nonjudgmental way and with due
consideration to confidentiality and trust cannot
be overemphasized.
Health care providers should help parents
explore and address their feelings when their
teens come out.
Cuisia-Cruz added that a type of disorder
that parents and pediatricians should be aware
of is gender dysphoria, formerly called gender
identity disorder. Gender dysphoria may be
manifested as strong desires to be treated as
the other gender or to be rid of ones sex char-
acteristics, or a strong conviction that one has
feelings and reactions typical of the other gen-
der. Teens with gender dysphoria are more at
risk for depression, suicidal ideation and suicide
attempts and anxiety disorders. She said that
patients with this condition should be referred
to mental health professionals as well as to a
pediatric endocrinologist.
READ JPOG ANYTIME, ANYWHERE.
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JUNE 2014 CONFERENCE COVERAGE 21
Football to help end malnutrition,
obesity in children
12th International Congress on Obesity, March 17-20, Kuala Lumpur, Malaysia
SARAS RAMIYA
F
ootball associations, corporations and foun-
dations are collaborating in a campaign to
end malnutrition and obesity among children in
Asia.
The Asian Football Confederation (AFC),
World Vision, DSM, Global Alliance for Improved
Nutrition (GAIN) and the Asian Football Devel-
opment Project have launched the One Goal
partnership with a vision of ensuring Nutrition
for Every Child in Asia.
While Asia is home to more than half of the
worlds malnourished children, the continents
burgeoning economies are faced with [anoth-
er] challenge affecting its children obesity,
said Stefan Germann, executive director of One
Goal, in a press release.
One Goal bring together powerful forces in
the region football, development and corpo-
rate expertise to address this issue and ensure
children eat, live and play right.
Asia is home to close to 578 million of the one
billion malnourished people around the world.
Some 100 million of the 165 million children glob-
ally who are stunted due to chronic undernutri-
tion are Asian. The region also faces a growing
challenge with obesity 7.7 percent of school-
age children are expected to be overweight in
2015 in ASEAN countries, an explosion from 1.8
percent in 1990. Obesity and poor nutrition prac-
tices also expose these same children to a higher
likelihood of contracting noncommunicable dis-
eases like diabetes and heart disease.
The One Goal campaign will seek to trans-
form child nutrition in Asia by engaging players,
fans and football lovers to become ambassa-
dors for good nutritional practices, and engage
and encourage governments to invest more in
helping children access nutritious foods so they
can grow up to be champions both on and off
the field.
The vision of the One Goal campaign is to
unite a diverse range of audiences under the
banner of football and serve them messages
about good nutrition, especially children, said
Tong Ngan Liew, CEO, World Vision Malaysia.
Malaysia is one of the first countries to launch
One Goal nationally. We are looking to ignite a
social movement that will transform child nutri-
tion in the region, helping more children survive
and thrive, he said.
MIMSmobileapp209x282_0314.indd 1 3/10/14 1:49 PM
JUNE 2014 CONFERENCE COVERAGE 23
Maternal malnutrition may infuence
obesity, diabetes risk in offspring
12th International Congress on Obesity, March 17-20, Kuala Lumpur, Malaysia
SEAH YEE MEY
T
he contentious issue of whether malnutri-
tion-related diabetes mellitus (MRDM) is a
distinct type of diabetes may have another vote
in its favor, based on results from a prospective
life-course study of mothers and their offspring
in India.
The ongoing Pune Maternal Nutrition Study
(PMNS) recruited 2,675 women of reproduc-
tive age between 1993 and 1996, and contin-
ued to follow the women who became pregnant
(N=814), as well as their offspring (N=770). As
of 2013, the 18th follow-up year of the study, the
PMNS cohort comprised 470 children and their
parents.
Mothers enrolled in the study were generally
small and thin, and their average weight, height
and body mass index were 42 kg, 1.52 m, and
18.1 kg/m
2
, respectively. Their offspring had rel-
atively low birth weights (average 2.7 kg), but
high adiposity, so-called thin-fat babies. By the
18th year, approximately 15 percent of the now-
adolescents were adipose (25 percent body
fat for boys and 35 percent for girls).
Extensive data, including body fat mass and
percentage, hyperglycemic status, and homeo-
static model assessments of -cells and insulin
resistance (HOMA-, HOMA-IR), were collected
from the PMNS participants every 6 years. Adi-
pose adolescents had higher fat mass (21.3 kg
vs 9.5 kg, as measured by dual-energy x-ray
absorptiometry) and percentage (35.3 percent
vs 20.2 percent) than non-adipose adolescents,
and more elevated HOMA-IR and HOMA-
scores, indicating increasing insulin resistance
and failure of -cells.
Interestingly, similar characteristics were al-
ready present in these offspring as early as 6
years into the study. While the differences in
the same measures were smaller at 6 years
than at 12 or 18 years, they were still signifi-
cantly higher (p<0.01) in the children who
were eventually adipose adolescents. At birth,
however, there were no significant differences
between the children with regards to weight,
length, subscapular and triceps thicknesses,
or placental weight. Pre-pregnancy character-
istics of PMNS-enrolled mothers were also not
significantly different.
Malnutrition during pregnancy impacts both mother and
child.
JUNE 2014 CONFERENCE COVERAGE 24
The glycemic statuses of a subset of the chil-
dren (N=308) were also recorded. Although 64
of them were hyperglycemic, they were neither
significantly heavier nor did they have more
body fat than the normoglycemic children when
measured at 6, 12 and 18 years. There were
also no differences at birth in gestation period
and neonatal size, nor were there pregnancy dif-
ferences in maternal size or intake of vitamins C
and D or iron. Notably, however, maternal intake
of calories, protein, carbohydrate, triglyceride
and vitamin B12 was lower in mothers of the hy-
perglycemic children.
The evidence produced by the PMNS is the
first demonstration of maternal malnutrition in-
fluencing offspring diabetes risk, said PMNS
researcher Dr. Chittaranjan Yajnik. Hale and
Barker first suggested the thrifty phenotype
hypothesis demonstrating that type 2 diabe-
tes is an outcome of nutritional thriftiness of the
fetus and early infant as indicated by low birth
weights. [Diabetologia 1992;35:595-601] WHO,
however, has yet to confirm their position on the
relationship between malnutrition and diabetes,
first creating the MRDM category in 1985, and
then withdrawing it in 1999, citing unconvincing
evidence for a causal link between malnutrition
or protein deficiency and diabetes.
While reasons behind the malnutrition-
diabetes correlation are still inconclusive, the
Pune Intervention Study was initiated in 2011 to
measure the effects of nutritional intervention.
Pregnant women were randomized to three
different arms: vitamin B12, 2 g only; vitamin
B12, 2 g in addition to multi-micronutrients;
and 20 g of milk powder, and iron and folate
tablets only; as per the guidelines for standard
care issued by the Indian government.
Babies of fasting mothers seem
smaller, but ftter
SARAS RAMIYA
P
renatal exposure to fasting during Rama-
dan may lead to smaller body size and im-
proved cardiovascular fitness in teenage boys,
shows a study.
Ramadan exposure during conception and
the third trimester of pregnancy may have long-
term consequences for body size and cardiore-
spiratory fitness (CRF) in adolescence, said As-
sistant Professor Tom Loney (Ph.D), Institute of
Public Health, College of Medicine and Health
Sciences, United Arab Emirates University, Al
Ain, United Arab Emirates (UAE).
The historical cohort study involved the en-
rolment data of 881 boys aged 14 to 18 from
a weekday residential school in Al Ain in 2008
and 2009. During enrolment and throughout the
academic program, the students had regular
anthropometric and fitness assessments.
JUNE 2014 CONFERENCE COVERAGE 25
To categorize individuals regarding their
exposure to Ramadan, we used passport-vali-
dated date of birth and assumed that concep-
tion took place 266 days before birth and their
mothers fasted during Ramadan. We also had
a group that was not exposed to Ramadan and
they were conceived about 68-70 days after Ra-
madan, said Loney.
The individuals were measured for height,
body mass, BMI and waist circumference, and
tested for fitness levels, ie, time taken to complete
a 1-mile run and their heart rate after the run.
Compared with the reference group, which
was not exposed during Ramadan (NER)
(n~190), the individuals who experienced Ra-
madan during the third trimester (R3T) (n=205)
had a lower BMI (-0.95 kg/m
2
; 95% CI -1.81,
-0.08, p<0.05) and smaller waist circumference
(-2.22 cm; 95% CI -4.42, -0.01, p<0.05), said
Loney.
Also, those conceived during Ramadan (CR)
(n=69) were slightly shorter (-2.16 cm; 95% CI
-3.96, -0.35, p<0.05) compared to those in the
NER group. Both the CR group (-47.4 s, 95%
CI, -77.3, -17.5, p<0.01) and R3T group (-22.2
s, 95% CI, -41.2, -3.2, p<0.05) completed the
1-mile run faster compared to the NER group,
he added.
So, there is biological plausibility for those
who experienced Ramadan during the third tri-
mester related to placental size and that has
been shown in a number of emerging cross-
sectional studies. We need to look for consis-
tency of evidence across research groups and
different populations, said Loney.
There is some emerging evidence that in ute-
ro exposure to intermittent fasting such as dur-
ing Ramadan may influence fetal programming
slightly differently and may have lasting health
consequences in offspring, he said.
A study in Tunisia has shown that babies ex-
posed to Ramadan in utero had slightly lower
birth weights, lower ponderal index and smaller
placental mass compared with those not ex-
posed. [Am J Hum Biol 2013;25:341-3]
Furthermore, a larger study in Indonesia
showed that adults exposed to Ramadan in ute-
ro were on average slightly shorter and lighter,
and had a lower BMI. Those who were conceived
during Ramadan also had similar features. [Am
J Epidemiol 2013;177:729-36]
Nevertheless, Loney emphasized that it is
too early to promote changes in the estab-
lished cultural practices of Ramadan fasting
based on current evidence. [Am J Epidemiol
2013;177:737-40]
Fasting practices may influence fetal programming.
JUNE 2014 CONFERENCE COVERAGE 26
21st Regional Congress of Dermatology, April 9-12, Danang, Vietnam
Older alopecia therapies still the
best supported
SEAH YEE MEY
D
espite emerging therapies for androgenet-
ic alopecia, currently available treatments
are still the most well-supported, says a derma-
tologist.
Androgenetic alopecia is the most common
form of hair loss in men and women, said Dr.
Nopadon Noppakun, professor of dermatology,
Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand. It is characterized by gradual
miniaturization of hair follicles in which the termi-
nal follicles are transformed into vellus-like hair.
This is accompanied by a decrease in the dura-
tion of anagen (growth phase).
The current gold standard for androgenetic
alopecia treatment is topical minoxidil (5 percent
for men, 2 percent for women), oral finasteride
(recommended for men only), or combination
therapy for men.
Early research into the mechanism of minox-
idil action suggested that it increases levels of
prostaglandin E2 in the scalp, thereby inducing
hair growth. [J Invest Dermatol 1997;108:205-
209] A balance between E2 and another pros-
taglandin, D2, appears to regulate hair growth
through the prostaglandin pathway and may
be responsible for hair loss in androgenetic
alopecia. [Sci Transl Med 2012;4:126ra34] Mi-
noxidil solution of 5 percent was shown to in-
crease hair growth in 57.9 percent of men 18
to 49 years of age (n=393) in 1 year. Interest-
ingly, 23.2 percent of the men who were given
placebo also had increased hair growth. [J Am
Acad Dermatol 2002;47:377-385]
Oral finasteride and dutasteride, which are
both 5-reductase inhibitors, have also been
proven effective in arresting progression of an-
drogenetic alopecia in men, as well as inducing
hair regrowth. [Skin Ther Lett 2012;17:1-4]
In a 2-year study of finasteride 1 mg/day in
men aged between 41 and 60 (n=424), 39 per-
cent of patients had increased hair growth, com-
pared with only 3 percent in the placebo group.
[Eur J Dermatol 2003;13:150-160] The long-term
efficacy of finasteride has also been studied in
118 men aged between 20 and 61; 86 percent of
the men benefited from the therapy, while 14 per-
cent worsened. [Dermatol Ther 2011;24:455-461]
Meanwhile, a randomized, placebo-con-
trolled trial comparing dutasteride and finaste-
ride in men aged between 20 and 50 (n=917)
found that dutasteride 0.5 mg/day significantly
increased hair count, width and growth at 24
weeks, and was statistically superior to finaste-
ride 1 mg/day and placebo. [J Am Acad Derma-
tol 2014;70:489-98]
Newer therapeutic agents for androgenetic
alopecia target various pathways involved in
hair growth such as the prostaglandin pathway
JUNE 2014 CONFERENCE COVERAGE 27
or the Wnt/b-catenin pathway; activation of Wnt
signaling is essential for hair follicle develop-
ment, hair cycling and growth. [J Invest Derma-
tol 2013;133:890-898]
Prostaglandin analogues such as latano-
prost or bimatoprost have been shown to in-
duce eyelash growth in patients. [Am J Oph-
thalmol 1997;124:544-547; J Am Acad Dermatol
2012;66:801-806] In a placebo-controlled pilot
study, latanoprost 0.1 percent was applied
topically in a small scalp area of patients with
androgenetic alopecia and found to significant-
ly increase overall hair density as well as the
number of vellus and terminal hair compared
with the placebo-treated area after 8 weeks. [J
Am Acad Dermatol 2012;66:794-800]
Lithium is another potential therapeutic agent
that appears to restore hair differentiation capa-
bility by increasing activity in the Wnt signaling
pathway. [Br J Dermatol 2012;166:1035-1042] Al-
though a trial to evaluate the effectiveness of topi-
cal lithium gluconate gel on hair follicle regrowth
has been carried out, said Noppakun, the results
have yet to be published.
JUNE 2014 CONFERENCE COVERAGE 28
21st Regional Congress of Dermatology, April 9-12, Danang, Vietnam
Two mycobacterial species
responsible for pretty leprosy
SEAH YEE MEY
I
nformally known as lepra bonita, meaning
pretty leprosy, a lepromatous leprosy variant
caused by the acid-fast bacillus bacteria Myco-
bacterium leprae has also been found to result
from infection by another related species, Myco-
bacterium lepromatosis.
M. leprae has long been known to be the
cause of leprosy; however, in 2008, a new spe-
cies, M. lepromatosis, was discovered in two
deceased Mexican patients who had variant dif-
fuse lepromatous leprosy, also known as Lucio-
Latapi leprosy. [Am J Clin Pathol 2008;130:856-
864]
Once limited to Central America, Lucio-Lata-
pi leprosy can now be found in other countries,
including Malaysia and Singapore. [J Drugs
Dermatol 2012;11:168-172] While M. leproma-
tosis appears to be the dominant cause of Lu-
cio-Latapi leprosy in Mexico and has also been
detected in patients in Singapore, only M. lep-
rae has so far been detected in Malaysian pa-
tients with Lucio-Latapi leprosy. [Int J Dermatol
2012;51:952-959]
Lucio-Latapi leprosy is characterized by dif-
fusely infiltrated shiny skin without nodules or
plaques (hence the nickname), with loss of eye-
brows and eyelashes. The diagnosis is often
only made when patients present with a necro-
tizing variant of erythema nodosum leprosum
also known as Lucios phenomenon.
Lucios phenomenon appears as intermit-
tent crops of well-defined, irregularly shaped
erythematous, purplish or purpuric macules
or patches most frequently found on the legs.
These skin lesions can evolve into hemorrhagic
infarcts or ulcers with ragged edges, and leave
atrophic scars after healing. Lucios phenom-
enon is usually only observed between 1 and
3 years after the manifestation of Lucio-Latapi
leprosy. Vasculitis has been established as the
cause of the painful red spots.
Other symptoms of Lucio-Latapi leprosy in-
clude peripheral neuropathy, destructive rhini-
tis, telangiectasia on the face and chest, livedo
reticularis, non-visible subcutaneous nodules,
widening of the nasal root and perforation of the
nasal cartilage. Differential diagnosis includes
septic vasculitis, cutaneous or systemic vascu-
litides, and other causes of thrombotic vascu-
lopathies. This is then confirmed by a positive
slit skin smear showing the presence of acid-
fast bacilli.
The WHO recommends multidrug therapy
with rifampicin, clofazimine and dapsone for the
treatment of multibacillary leprosy, said senior
consultant dermatologist, Dr. Choon Siew Eng.
Severe reactions should be treated with a sys-
temic steroid like prednisolone.
JUNE 2014 RESEARCH REVIEWS 29
Pharmacies feasible screening sites for individuals at risk
of diabetes, CVD
T
he increasing prevalence of diabetes and
cardiovascular disease (CVD) has led to
numerous studies of interventions aimed at pre-
vention, including community-based screening
of individuals at risk. Community pharmacies are
feasible sites for such interventions, but further
research into methods for increasing uptake of
follow-up testing are required, say the authors
of a recent systematic review and meta-analysis.
They undertook a systematic search of the
Cochrane central register of controlled trials
and the MEDLINE and EMBASE databases and
identified 16 pertinent articles published be-
tween 1950 and 2012 that altogether assessed
108,414 subjects (mean age 54.6 years, 56.6
percent female) who were screened for CVD risk
factors such as cholesterol, blood pressure, and
type 2 diabetes mellitus.
The researchers found that pharmacies were
feasible sites for screening individuals at risk of
diabetes and CVD, as a significant number of
subjects with previously undiagnosed risk factors
such as hypertension, hypercholesterolemia,
and diabetes were identified. However, all of the
included studies reported high rates of attrition
between pharmacy screening and follow-up as a
significant number of referred high-risk individu-
als did not attend their primary practitioner for
further follow-up examinations.

Wills et al. The effectiveness of screening for diabetes and cardio-
vascular disease risk factors in a community pharmacy setting.
PLoS ONE 9(4): e91157. doi:10.1371/journal.pone.0091157
JUNE 2014 RESEARCH REVIEWS 30
New predictive models needed for de novo metastatic breast
cancer in Asians
T
he number of Asian breast cancer patients
who present with distant metastases at the
time of diagnosis is much greater than in Europe
or the US, and a recent systematic review has
suggested that this is because existing predic-
tive models do not have sufficient discriminatory
power in Asian populations.
The researchers identified 16 predictive mod-
els by searching the MEDLINE and EMBASE
databases and assessed the validity of the se-
lected models using data from 642 women in
the Singapore Malaysia Hospital Based Breast
Cancer Registry who were diagnosed with de
novo metastatic breast cancer between 2000
and 2010. Survival curves for patients deemed
to be at low, intermediate, or high risk of metas-
tases according to the prognostic scores de-
rived from each model were compared by log-
rank test and the discrimination ability of each
model was assessed by concordance statistic
(C-statistic).
Performance status, estrogen receptor sta-
tus, metastatic site(s), and disease-free inter-
val were revealed as the most common prog-
nostic indicators and nine of the prediction
models were validated. However, the ability of
the models to discriminate between poor and
good survivors was modest (C- statistic range
0.50-0.63).
The researchers concluded that an Asian-
specific prediction model was required to im-
prove prognostication.
Miao et al. Predicting survival of de novo metastatic breast cancer
in Asian women: systematic review and validation study. PLoS
ONE 9(4): e93755. doi:10.1371/journal.pone.0093755
JUNE 2014 RESEARCH REVIEWS 31
T
he suggestion that breast cancer risk is in-
creased by suppression of nocturnal mela-
tonin production remains controversial. A recent
case-control study found no significant asso-
ciation between levels of 6-sulfatoxymelatonin
detected in pre-diagnostic first-morning urine
samples and subsequent breast cancer risk,
but a meta-analysis performed by the same re-
searchers indicated that higher 6-sulfatoxymela-
tonin levels were associated with a reduction in
breast cancer risk.
The case-control study was performed using
data from 251 breast cancer patients and 727
matched controls, all of whom were participants
in the British Guernsey III cohort study (1977
2009). The meta-analysis included findings from
the case-control study combined with other pro-
spective data derived from studies published
before October 31, 2012 and identified by a
PubMed search using the keywords breast
cancer, melatonin, and 6-sulfatoxymelato-
nin. The final analysis included 1,113 patients
with breast cancer and 2,944 matched controls
from five studies.
When findings from all of the studies were
combined, women in the highest quartile of uri-
nary 6-sulfatoxymelatonin concentration were
found to have a reduced risk of breast cancer
compared with those in the lowest quartile (ag-
gregate odds ratio [OR] 9.81, 95% CI 0.660.99).
However, further analysis indicated that this only
Melatonin suppression linked to breast cancer risk?
held true for postmenopausal (OR 0.68, 95% CI
0.490.92) and not premenopausal (OR 1.05,
95% CI 0.711.54) women.
The researchers conclude that further data
are needed to confirm an association be-
tween melatonin levels and breast cancer
risk.
Wang XS et al. First-morning urinary melatonin and breast cancer
risk in the Guernsey study. Am J Epidemiol 2014;179:584-593
JUNE 2014 RESEARCH REVIEWS 32
N
umerous studies have demonstrated the
anticancer potential of mushrooms and a
recent review has provided further evidence of
the association between dietary mushroom in-
take and a reduction in breast cancer risk.
Searches of PubMed, Web of Science, and
Google Scholar using the keywords mushroom
or fungi and breast cancer, breast carcino-
ma, breast tumor or breast tumour identified
eight case-control studies performed in Asian
countries (2,313 cases with 2,387 controls) and
two cohort studies performed in Europe (4,577
cases with 1,748,623 person years of follow-up).
The total number of cases was 6,890.
Dose-response analysis of the data did not
reveal any non-linear association between
mushroom consumption and breast cancer
risk (p=0.337) and a 1 g/day increment in
mushroom intake was associated with a rela-
tive risk of 0.97 (95% CI 0.960.98) for breast
cancer. When the analysis was based on meno-
pausal status, the relative risk was 0.96 (95%
CI 0.911.00) for premenopausal women and
0.94 (95% CI 0.91097) for postmenopausal
women. The researchers note that large-scale
Edible mushrooms may reduce the risk of breast cancer
prospective studies are required to confirm
these findings.
Li et al. Dietary mushroom intake may reduce the risk of breast
cancer: evidence from a meta-analysis of observational studies.
PLoS ONE 9:e93437. doi:10.1371/journal.pone.0093437
JUNE 2014 AFTER HOURS 33
An adventure in exotic
SOUTH AMERICA
Rafael Mendoza, Economist Healthcare Expert and World Traveler
S
outh America is probably not a very common destination
to consider when we are planning for our next holidays.
However with Brazil hosting the football world cup, many
doctors in Asia are starting to look at this continent as an
option that is equally as mysterious, seducing and full of
energy as it is far.
In my experience, traveling the world with low to mid size
pockets, I concluded the best way to know a place is through its people and food. Latino-Amer-
icans are very well known for their hospitality and friendly character, hence travelers of all bud-
gets will not have any difficulty getting to know the culture, making a good local friend, be invited
to someones house, or even dancing the typical music with a free-of-cost, dedicated teacher.
The gastronomic options and the activities list could be large and overwhelming. Here I will only
give you three destinations of the many must visits if you are considering crossing the Pacific to
the very west of the globe.
L
ets start our journey in South America from north to south.
If you like snorkeling, scuba diving or just relaxing at a paradi-
siacal beach, then you need to make a stop in Los Roques, Ven-
ezuela.
Los Roques has been ranked number one in the world by the
magazine Mens Health for the top five beaches you must visit.
You can choose to stay on a yacht, a sailing boat, an economical or 5-star lodge on the main
island. Once in Los Roques you can eat freshly caught lobster which you can even try to fish for
it yourself. Just ask one of the locals or foreign locals to prepare it for you.
Los Roques is home to people from all over the world. The new locals have brought much of
their own style and cooking recipes with them, many of which have been adapted or fused with
local flavors, resulting in an amazing blend of nature and gastronomy.
LOS ROQUES, VENEZUELA
JUNE 2014 AFTER HOURS 34
I
f your passion is not the
beach but the mountains
and hiking, then the Inca Trail
in Peru should be a manda-
tory part of your trip to South
America. The Inca Trail is by
far the most famous trek on
the continent. It is a UNESCO
World Heritage site and one of
the seven marvels of the world.
The final destination of the trail
cannot be beaten: Machu Picchu, the mysterious Lost City of the Incas.
The Inca Trail is just a small stretch of the entire network of Inca roads that ran all over the
territory. This particular stretch is important because it links various sites. It is believed that the
Spaniards did not discover this trail as it was too difficult for their horses to get through allowing
it to be preserved.
Lonely Planet has described a visit to the Inca Trail as a life-changing experience. Hiking
the through the Sacred Valley to Machu Picchu is both arduous and awe-inspiring. Four days
of cold, pain and exhaustion dissipate as the mist lifts to reveal the emerald peaks and terraced
ruins of the mystical ancient city.
Peru has been named the Worlds Leading Culinary Destination for 2 years running by the
World Travel Awards. The best recommendation I can give in terms of what to eat in Peru is to
try a variety eat small portions of five to six different plates throughout the day. Everything is
delicious and you might not have time to try it all.
INCA TRAIL,
PERU
RIO DE JANEIRO, BRAZIL
O
f course no visit to South America is quite complete
without a visit to vibrant Rio de Janeiro in Brazil.
While the list of places to visit in Rio is long, one should
try to go and do everything that is well known and recom-
mended: Take a tour to see Corcovado or ride the cable
car up to the Sugarloaf Mountain. Spend a day at Copa-
cabana (where all you need is attitude and a little bit of
sun screen).
JUNE 2014 AFTER HOURS 35
Most importantly, Rio de Janeiro is one of the sexiest cities in the world. People are passion-
ate about life, not shy, and commonly talk to strangers like life-long friends. They proudly show
their tanned and a spectacular bodies and enjoy every aspect of life. There is no need for an
excuse to celebrate and taste all the varieties of Caipirinhas, dance all day and night, and laugh.
If after all this you have time for food, Brazil is famous for its Churrasquerias an all-you-
can-eat barbeque where you can indicate if a server needs to continue serving non-stop or you
need a little break. You will enjoy all kind of appetizers, salads and complements, but dont lose
the focus the meat is spectacular.
All in all, traveling in this developing part of the world Latin America allows one to discover
well kept secrets as well as understand more the untapped needs for those striving for greater
opportunities. I find this very inspiring and it has helped me to approach my work and projects
from a more humanistic perspective.
Have a great trip to South America and drink good rum, a good Pisco and Caipirihna in my
name.
JUNE 2014 HUMOR 36
I must warn you doctormy husband and
science seldom see eye to eye!
We can iron out the wrinkles
on your face and neck, but we
recommend plastic surgery.
It would be safer and much
less painful!
The vet will see you now!
I have bad and good news.
The bad news is we dont know
whats wrong with you. The
good news is the circus is in
town and they are hiring!!
Now, before we go any furthershall we agree
theres no use kidding ourselves?
Do you consider yourself
an emergency?
P U B L I S H E R
Ben Yeo
MA N A G I N G E D I T O R
Greg Town
S E N I O R E D I T O R
Christina Lau
C O N T R I B U T I N G E D I T O R S
Jackey Suen, Jenny Ng (Hong Kong),
Saras Ramiya, Pank Jit Sin, Malvinderjit Kaur
Dhillon (Malaysia), Dr. Maria Katrina Florcruz,
Dr Mei Beluan (Philippines), Radha Chitale,
Elvira Manzano, Chuah Su Ping ,Grace Ling
(Singapore)
P U B L I C AT I O N MA N A G E R
Marisa Lam
D E S I G N E R S
Razli Rahman, Anson Suen, Lisa Low,
Joseph Nacpil, Agnes Chieng, Sam Shum
P R O D U C T I O N
Edwin Yu, Ho Wai Hung, Jasmine Chay
C I R C U L AT I O N E X E C U T I V E
Christine Chok
A C C O U N T I N G MA N A G E R
Minty Kwan
A D V E RT I S I N G C O - O R D I N AT O R
Rachael Tan
P U B L I S H E D B Y
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