NEWS & INSIGHTS MALAYSIA • 1-15• APR

MALAYSIA 1-15 2015

APR 2017

Dosage monitoring of
aminoglycosides helps reduce
hearing loss in MDR-TB

SPOTLIGHT MALAYSIA FOCUS

High-dose rifampicin Increased IV fluid intake
regimen may offer may reduce need for
shorter, safer treatment caesareans
for TB

REGIONAL INTERNATIONAL
Chinese patients with Predictor of cardiac
diabetes may lose 9 function linked to low-
years of life grade exercise tolerance
in COPD

Dosage monitoring of
aminoglycosides helps reduce
hearing loss in MDR-TB
PEARL TOH
L owering the dosage of aminoglycosides
guided by therapeutic dose monitoring
(TDM) appears to reduce aminoglycoside-re-
lated hearing loss, without compromising its ef-
ficacy against multidrug resistant tuberculosis
(MDR-TB), a recent study suggests.
The retrospective study included 80 pa-
tients (mean age, 30.5 years, 53.8% male) with
culture-confirmed MDR- or extensively drug
resistant-tuberculosis, who received the ami-
noglycosides kanamycin or amikacin for at
least 3 days as part of their treatment regimen.
Out of these, 57 patients whose blood sample
data were available were analyzed. [Antimi-
crob Agents Chemother 2017;doi:10.1128/
AAC.01400-16]
All patients (except one) were started on a
standard, individual dose of aminoglycoside
(median daily dose, 400.0 mg, inter-quartile
range [IQR], 60–111) for a median duration of
85 days. Drug dose was subsequently adjusted
as guided by routine TDM of their serum ami-
kacin or kanamycin levels and the maximum
concentration (Cmax) to mean inhibitory concen-
tration (MIC) ratio (Cmax/MIC) of their sputum
isolates.
After treatment, 35 patients (67.3%) were
successfully treated, with no relapses over 2
1-15 APRIL 2017 • 2
years of follow-up. The median dose used was
higher in male compared with female patients
(6.7 vs 6.0 mg/kg; p=0.025) for both kanamy-
cin and amikacin.
“The dosage applied in our study is twofold
lower than the 15 mg/kg recommended by the
World Health Organization, yet outcome was
favourable in the vast majority of patients,” ac-
cording to the researchers. “In those with un-
favourable outcome, aminoglycoside dosage
appeared unrelated to those outcomes.”
In 70 patients with available audiometry re-
sults, hearing loss occurred in nine patients
(11.3%) mainly at higher frequencies of 4000 to
8000 Hz after aminoglycoside treatment, which
was lower than the 37% incidence rate after
treatment and 21.3% incidence rate during
treatment reported in previous studies. [Clin In-
fect Dis 2004;38:1538–1544; J Tuberc Lung Dis
2002;6:622–627]

“We therefore hypothesize that the dose of
aminoglycosides can be decreased, taking into
consideration that the Cmax/MIC recommenda-
tions are met, when co-administrated with oth-
er highly active medication, such as linezolid,
clofazimine and moxifloxacin, without apparent
loss of efficacy,” suggested the researchers.
Noting that the use of aminoglycosides for
MDR-TB treatment was often associated with
profound and permanent toxicity such as hear-
ing loss, the researchers urged that audiometry
should be performed regularly.
They also recommended that dosing should
MD 1_3 Delfi Prospan_Mar8.pdf 1 08/03/2017
1-15 APRIL 2017 • 3
be based on Cmax/MIC of aminoglycosides in-
stead of body weight for improving treatment
outcomes and reducing toxicity, adding that
“therapeutic parameters, particularly dose, cu-
mulative dose, duration and Cmax, were all non-
significantly correlated with ototoxicity; making
ototoxicity prediction with these parameters not
possible.”
As this is a retrospective study, the research-
ers acknowledged that the efficacy and safety
of using a TDM-guided lower dosage of amino-
glycoside should be further investigated in ran-
domized controlled trials.
7:30 PM

High-dose rifampicin regimen may
offer shorter, safer treatment for TB
ANGELA IGNACIO
R ifampicin at a dose of 35 mg/kg reduces
the time to culture conversion in liquid me-
dia and may therefore be a potentially useful
component for shorter regimens in the treat-
ment of tuberculosis (TB), according to a re-
cent study. [Lancet Infect Dis 2017;17:39–49]
The randomized controlled, open-label trial
included 365 patients with newly diagnosed,
rifampicin-sensitive and previously untreated
pulmonary TB from various health centres in
South Africa and Tanzania.
Experimental treatment consisted of four dif-
ferent arms: rifampicin 35 mg/kg, isoniazid, pyr-
azinamide and ethambutol (n=63); rifampicin
10 mg/kg, isoniazid, pyrazinamide and SQ109
1-15 ARPRIL 2017 • F O R U M • 4
300 mg (n=59); rifampicin 20 mg/kg, isoniazid,
pyrazinamide and SQ109 300 mg (n=57); and
rifampicin 20 mg/kg, isoniazid, pyrazinamide
and moxifloxacin 400 mg (n=63). A daily stan-
dard regimen of 10 mg/kg rifampicin, 5 mg/
kg isoniazid, 25 mg/kg pyrazinamide and 15
to 20 mg/kg ethambutol was used as control
(n=123). Experimental treatment was given for
12 weeks, followed by 14 weeks of standard
dose isoniazid and rifampicin.
The primary analysis included patients with-
out phenotypic evidence of rifampicin resis-
tance and who took at least one dose of study
treatment and had one positive culture on liq-
uid or solid media before or within the first 2
weeks of treatment. The primary endpoint was
time to sputum culture conversion in liquid me-

dia within 12 weeks.
Compared with the control group, the 35
mg/kg rifampicin group had a shorter median
time to stable conversion in liquid media (48 vs
62 days; adjusted hazard ratio, 1.78; 95% CI,
1.22 to 2.58; p=0.003). This was not observed
with the other experimental arms. On solid me-
dia, no difference in time to culture conversion
was observed in any of the groups.
Approximately 45 (12%) of patients reported
1-15 ARPRIL 2017 • F O R U M • 5
grade 3 to 5 adverse events, which was similar
across all arms.
As prespecified efficacy thresholds were not
met at the planned interim analysis, recruitment
was stopped early in the two arms containing
SQ109. Also, researchers noted that masking
of patients and clinicians to treatment arms
was not possible due to the presence of or-
ange discoloration of body fluids observed with
higher doses of rifampicin.

Possible link between vitamin D deficiency, autoimmune
thyroid disease
V  itamin D may be a useful addition to treat-
ment protocols for autoimmune thyroid
diseases such as autoimmune encephalomy-
elitis, rheumatoid arthritis, systemic lupus ery-
thematosus, type 1 diabetes, and inflammatory
bowel disease, according to a recent prospec-
tive study conducted in Turkey.
The researchers randomized 82 patients with
such diseases who were also deficient in vita-
min D (defined as serum values <20 ng/mL) to
vitamin D 1000 IU/day (n=46) or no such sup-
plement (n=36, controls) for one month. Serum
thyroid-stimulating hormone, free T4, thyroid
peroxidase antibody (TPO-Ab), thyroglobulin
antibody (TgAb), and vitamin D levels were as-
sayed before and immediately after treatment.
Compared with baseline values, serum lev-
1-15 APRIL 2017 • M E D I C A L B R I E F S • 6
els of TPO-Ab (267.9 IU/mL vs 278.3 IU/mL,
p=0.02) and TgAb (274.5 IU/mL vs 331.9 IU/
mL, p=0.03) were significantly reduced, and
levels of vitamin D significantly increased (11.5
ng/mL vs 21.4 ng/mL; p<0.001), among pa-
tients treated with vitamin D.
No such changes were observed among the
controls. Thyroid function was not significantly
changed by vitamin D replacement.
The researchers remarked that the decrease
in thyroid antibody titres observed among pa-
tients in the treatment group suggests that vita-
min D supplementation may be a useful auxil-
lary treatment for such patients. However, they
cautioned that further studies are required to
elucidate the mechanism responsible for such-
changes.

Brain stem volume may be linked to aggression
in autism
S maller brain stem volume may be linked
to aggression in children with autism, ac-
cording to US-based researchers.
They examined magnetic resonance imag-
ing (MRI) images of the brains of 45 male chil-
dren with autism who were grouped according
to whether or not they showed problematic lev-
els of aggression. Images from both groups of
children were also compared with MRI images
taken from 18 male children without autism.
Although the researchers determined the
volume of the brain stem, amygdala, orbito-
1-15 APRIL 2017 • M E D I C A L B R I E F S • 7
frontal cortex, anterior cingulate cortex, and
dorsolateral prefrontal cortex, only brain stem
volume was found to be predictive of aggres-
sion. Children who had smaller brain stem vol-
umes were more likely to be in the group with
problematic aggression.
The researchers suggest that their findings
can help inform treatment approaches for af-
fected children, but stress that further research
is required to identify possible mechanisms by
which arousal and aggression may be linked to
brain stem structure and function.
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Increased IV fluid intake may
reduce need for caesareans
RACHEL SOON
P roviding more intravenous (IV) hydration
during labour could reduce the frequency
of caesarean operations, according to a new
study.
In a meta-analysis of seven randomized
control trials encompassing 1,215 first-time
mothers, it was found that women receiving IV
fluids at 250 mL/hour had a significantly lower
incidence of caesarean delivery versus those
receiving the general USA standard of 125 mL/
hour. (12.5% vs 18.1%; RR 0.70, 95% CI 0.53–
0.92) [Acta Obstet Gynecol Scand 2017;doi:
10.1111/aogs.13121]
“The results are compelling and strongly ar-
gue for a change in practice,” said Dr. Vincenzo
Berghella, lead author and professor of obstet-
rics and gynaecology at Thomas Jefferson
University. “We have already begun changing
practice at Jefferson to give women more fluids
in labor, to allow them to have the best chance
of delivering vaginally.”
Of the 1,215 women, 593 received IV fluids
at 250 mL/hour, while the remainder received
them at half the rate. IV fluids were reported ei-
ther as lactated Ringer’s solution (five studies),
normal saline in dextrose water (one study) or
unknown (one study).
Notably, no significant reduction in inci-
dence of caesarean delivery was reported in
those women who were able to drink during
1-15 APRIL 2017 • M A L AYS I A F O C U S • 9
labour.
“It has been known for some time that hy-
dration in labour improves outcome,” said Dr.
Raman Subramaniam, consultant obstetrician
and gynaecologist, commenting on the study.
He added: “[However] we don’t routinely set
up a drip in labour, except for an epidural or
in cases of increased risk of post-parturition
bleeding.”
Raman also added that while women should
be given IV in labour if necessary, IV use should
be implemented cautiously as it requires close
monitoring by nurses to avoid air infiltration
once the pack has emptied.
The same study also found that the women
receiving higher IV fluid rates had shorter over-
all labour duration by around 1 hour, regard-
less of fluid type used (mean difference -64.38
minutes, 95% CI -121.88 to -6.88; 6 studies,
1,155 participants).
Evaluating local operation rates
Data collated from various MOH databases in-
dicates that caesarean rates in Malaysia have

been steadily increasing; the 2014 Annual Re-
port notes that caesareans accounted for 21%
of public hospital births that year, in contrast to
10.5% in 2000 and 15.7% in 2006. [Med J Ma-
laysia 2008;63(5):434–435]
According to Professor Dato’ Dr. Ravindran
Jegasothy, former head of obstetrics and gyn-
aecology at Hospital Kuala Lumpur and au-
thor of several publications on local caesarean
rates, the 2014 rate for private hospitals was
even higher at 31.4% (unpublished data).
“The total number of deliveries in all sectors
(in 2014) was 476,476, making a caesarean
section rate of 22.4%,” said Ravindran. “What
was striking was the rate of LSCS [lower seg-
ment caesarean section] was markedly lower
in the states of Kelantan, Terengganu and to
some extent Pahang (11–13%) in the private
sector. There is obviously a need to study this
discrepancy in depth and to learn lessons from
this.”
With rising rates a global trend, Ravindran
Company seeks to improve access to
legitimate online medical opinions
DR. JOSLYN NGU
W ith the introduction of a second medical
opinion online platform late last year, Ma-
laysians will now be able to get additional med-
ically sound advice from specialists through the
1-15 APRIL 2017 • M A L AYS I A F O C U S • 10
noted that the decision to undergo the proce-
dure often depends on an obstetrician’s deci-
sions based on the mother’s risk profile, with
the final decision made by the mother but
based on the advice of the obstetrician.
“There is great concern for the status of the
unborn child in the decision making,” said Ra-
vindran. “It cannot be denied that the medico-
legal situation also plays a role; there can be
a defensive practice by obstetricians in opting
for caesarean delivery rather than a normal de-
livery.
In 1985, WHO guidelines advised for a target
caesarean rate of 10 to 15%. However, a more
recent revision has emphasized that “[C-sec-
tions] should be undertaken when medically
necessary, and rather than striving to achieve a
specific rate, efforts should focus on providing
caesarean section to all women in need … [as]
ascertained by the health care providers car-
ing for the woman on a case-by-case basis.”
[BJOG 2016;123:667–670]
internet.
Speaking at the media briefing event, man-
aging director and cofounder of Medical Opin-
ion Asia, Stuart J. Venner said there are too
many instances where patients turn to online
sites and total strangers for medical advices,

and believe them readily without performing
any background check. This is dangerous and
a reliable source of medical advice is neces-
sary. That is where the company’s online plat-
form comes into the picture.
The online platform provides patients a has-
sle-free way to obtain a second opinion before
embarking on a treatment plan or simply to put
their mind at ease, said Venner. “There is total
confidentiality and patients can get opinions
from our medical specialists without the usual
effort and time spent at a conventional medical
appointment,” he added.
Tan Sri Dato’ Dr. Aseh Hj Che Mat, chairman
of Medical Opinion Asia, who was also speak-
ing at the event, said the online service is com-
mendable as it is a digital healthcare business
that combines current and future technology.
The online platform is equipped with advanced
software to enhance its services and to move
high quality medical images.
Besides second opinions, the online service
also extends to include concierge and data
storage services. The online portal has a user-
friendly and sophisticated platform for patients
to upload their medical records and images.
Cardiologist Dr. David Charles Cumberland, di-
rector and clinical advisor of Medical Opinion
Asia, said imaging results from coronary angio-
grams uploaded by patients onto the platform
1-15 APRIL 2017 • M A L AYS I A F O C U S • 11
are very clear, making it similar to watching a
live coronary angiogram. This makes diagnosis
an easier process for the doctors.
“We are very fortunate to have top medical
specialists from major private hospitals and
medical centres with us,” said Venner. Current-
ly, there are 50 medical specialists on the plat-
form’s panel, covering cardiology, orthopaedic
surgery, radiology, sports medicine and neuro-
surgery, among others.
The American Heart Association states a
number of reasons for obtaining a second
opinion, such as if the patient is feeling rushed
or not confident in the doctor’s decision. Other
reasons include it being a requirement by some
insurance policies and if the patient has several
treatment alternatives to consider. [Available
at: www.heart.org/HEARTORG/Conditions/
More/MyHeartandStrokeNews/Getting-a-
Second-Medical-Opinion_UCM_434325_Ar-
ticle.jsp#.WK0-KNJ96M8]

Top-down approach for a smoke-
free workforce
DR. JOSLYN NGU
A smoke-free workforce initiative that ap-
peals to organization leaders and pioneers
from top corporations to be directly involved
in championing the cause for a healthier and
smoke-free workforce has been launched lo-
cally.
The initiative is a first-of-its-kind smoking
cessation initiative. Its target audience are adult
smokers who are currently in the workforce.
Working adults are important contributors to
the economy and are every organization’s big-
gest asset. As such, making an effort to im-
prove employee’s well-being will be a win-win
situation for both the employees and company,
said Chin Keat Chyuan, managing director of
Johnson & Johnson (J&J) Malaysia, who was
speaking at the launch of the initiative. “At J&J,
we are constantly dedicated to discovering
ways to improve the health and quality of life.
We understand that smokers need support and
assistance to quit.”
J&J Malaysia’s efforts in the initiative include
subsidizing pharmacotherapy starter kits, pro-
viding a health talk and information booths—
with a smokerlyzer test made available—at par-
ticipating companies. “By providing cessation
activities and offering a healthy, smoke-free
work environment, employers can help their
employees quit smoking,” said Chin.
Additionally, the company plans to initiate a
1-15 APRIL 2017 • M A L AYS I A F O C U S • 12
new employee ben-
efit scheme for all
J&J Malaysia em-
ployees and their
immediate family
members: all smok-
ers will be offered
the opportunity to
join a smoking ces-
sation programme assisted by trained health-
care providers and equipped with counselling
services.
The launch was officiated by the health min-
ister, Datuk Seri Dr. S. Subramaniam, who said
the MOH has always been actively involved in
smoking cessation programmes. For instance,
in 2015, a nation-wide programme called the
M Quit Services was implemented to provide
smoking cessation services in public and pri-
vate health institutions. The programme was of-
ficiated under a Memorandum of Understand-
ing between the MOH, J&J, Universiti Sains
Malaysia, University of Malaya and the Malay-
sian Academy of Pharmacy.
According to the 2015 National Health and
Morbidity Survey, around 4.9 million Malay-
sians above the age of 15 are smokers. Half
attempted to quit smoking but only one-in-10
visited appropriate healthcare providers for
support to do so. The Smoke-free Workforce
initiative aims to help 2% of the estimated 4.9
million smokers to quit smoking each year.

Antibacterials frequently linked to
adverse drug reactions in infants
RACHEL SOON
A ntibacterial drugs may account for two-
thirds of adverse drug reactions (ADRs) in
Malaysian children under 2 years of age, a new
study suggests.
In a retrospective analysis of 11,932 reports
of ADRs in children received by the Malay-
sian National Pharmaceutical Control Bureau
(NPCB) from 2000 to 2013, researchers from
Universiti Teknologi MARA (UITM) identified
1,667 reports (14.1% of total) related to chil-
dren under 2 years. Of the ADRs analysed in
this age group, antibacterial drugs for systemic
use accounted for 61.9%. [Front Pharmacol
2017;doi:10.3389/fphar.2017.00030]
“The majority of ADRs were subacute reac-
tions that occurred within 24 hours of exposure
to the drug,” the authors noted. “A high propor-
tion of ADRs was classified as mild, and most
victims had no sequela.”
The most common ADRs reported were skin
appendage disorders (60.1%), categorized as
rash (n=215), maculopapular rash (n=206),
urticaria (n=169), erythematous rash (n=76),
and pruritus (n=58). The authors added that
the common usage of antibiotics among this
age group could account for its frequent as-
sociation with ADRs, in addition to a general
increased vulnerability due to their stage of
physiological development.
Of the causal antibacterials identified, peni-
1-15 APRIL 2017 • M A L AYS I A F O C U S • 14
cillin was the most commonly recurring (30.3%
of all ADRs), followed by other β-lactam anti-
bacterials (13.6%); macrolides, lincosamides
and streptogramins (6.0%); and aminoglyco-
sides (3.5%).
Exclusion criteria from the study included
patients being older than 2 years; ADRs with
causality evaluated as neither certain, possible
nor probable; ADRs due to drug administration
to the mother; non-citizen; non-drug products;
reports with no information on ADR onset); and
miscellaneous/others . After exclusion criteria,
only 907 ADR reports (neonates, n=109; in-
fants, n=798) remained for analysis, covering
1,667 ADRs.
Issues in ADR reporting
In discussing the results, the authors ac-
knowledged that their data was limited to the
NPCB’s spontaneous reporting database, and
that ADRs among children under 2 years old
could be underreported therein. A previous

study by the same team found that the age
group accounted for only 12.8% of reports to
the NPCB between 2000 and 2013 for ADRs
in patients aged 0 to 17 years. [PLoS One
2016;11(6):e0155385]
In addition to this, they highlighted that more
than 90% of ADR reports they were able to ob-
tain were submitted from healthcare profes-
sionals in the public sector, with the majority
from pharmacists (51.4%), followed by doctors
(38.7%).
“Active surveillance studies should be con-
Hand hygiene still key to mitigating
HFMD epidemics
RACHEL SOON
P roper disinfection of hands and surfaces re-
mains the main weapon to stem outbreaks
of hand, foot and mouth disease (HFMD), ac-
cording to a virologist.
“The HFMD viruses are highly contagious as
they spread easily through physical contact or
from contaminated surfaces,” said Privatdozen-
tin Dr. Maren Eggers, head of Virology and Dis-
infectant Testing at the Labor Prof. G. Enders
& Partner, Germany. “As antivirals and vaccines
are not available (for HFMD), basic hygiene is
the only way to prevent infection.”
Since the first locally recorded outbreak of
HFMD in 1997—resulting in 41 fatalities among
1-15 APRIL 2017 • M A L AYS I A F O C U S • 15
ducted in the Malaysian paediatric population
since our findings as well as studies reported
by Rashed et al. have shown relatively high
rates of ADRs experienced by pediatric inpa-
tients in Malaysia,” wrote the authors. “Future
studies monitoring ADRs should be undertak-
en in a real hospital setting involving neonates
and children under 2 years of age, as this study
observed only a small number of ADRs for this
group being reported to the national pharma-
covigilance system.” [Eur J Clin Pharmacol
2012;68:801–810]
infants and young children in Sarawak—epi-
demics have struck Malaysia in cycles of 2 to
3 years, with a majority of cases attributed to
Enterovirus 71 (EV-71) and Coxsackievirus A16
(CVA16). One of the most severe national epi-
demics occurred in 2016, during which 23,454
cases were reported by the MOH between

January and August. [Virol Sin 2011;26(4):221–
228]
Transmission of HFMD occurs via direct
contact with infected bodily fluids, blister fluids
and faeces. After an incubation period of 3 to
5 days, HFMD’s initial symptoms include fever,
poor appetite, malaise, and sore throat. Within
1 to 2 days of initial symptoms, small, pain-
ful oral sores develop, beginning as small red
spots which may blister and become ulcers.
Non-itchy blister-like rashes subsequently form
on the hands, feet and mouth, as well as the
buttocks and genitalia in some cases.
“Most mild HFMD patients recover fully after
the acute illness in 7 to 10 days,” said Eggers.
“However, there are severe cases of HFMD in
which patients develop viral meningitis or en-
cephalitis or even poliomyelitis-like paralysis,
and may need to be hospitalized for several
days.”
Speaking at the recent launch of an anti-
septic skin cleanser in Kuala Lumpur, Eggers
cautioned that alcohol and phenolic disinfec-
tants—typically used in hand sanitizers—lack
efficacy against non-enveloped viruses such
as the enteroviruses which cause HFMD, and
recommended active ingredients with proven
1-15 APRIL 2017 • M A L AYS I A F O C U S • 16
virucidal effect, such as povidone-iodine. She
added that as viral loads persist in the stools
of recovered patients for up to 2 months, main-
taining strict disinfection practices is paramount
during seasonal epidemics.
A recently published study of 2,141 EV-71
antibody-positive serological samples from a
single Malaysian hospital—collected from 6
outbreaks between 1995 to 2012—found that
outbreaks coincided with the accumulation
of a pool of non-immunized children between
epidemics, as well as an increase in the virus’s
genetic diversity among the population. Inci-
dence rates were highest among children be-
tween ages 0 to 2 years, though children up to
13 years old were also susceptible to the dis-
ease. [PLoS Negl. Trop. Dis 2016;doi:10.1371/
journal.pntd.0004562]
Vaccine development remains challenging
due to the genetic diversity of the causative vi-
ruses; however, an inactivated whole virus vac-
cine against EV71 was approved in 2015 by
the China Food and Drug Administration, and
development of other vaccines is underway in
several Asia-Pacific countries including Singa-
pore and Taiwan. [Vaccine 2016;34(26):2967–
2970]

Chinese patients with diabetes may
lose 9 years of life
DR. JOSEPH DELANO FULE ROBLES
A recent 7-year study of more than 500,000
Chinese adults reported that diabetes is
associated with increased mortality from car-
diovascular and noncardiovascular causes.
Compared with adults without diabetes, indi-
viduals with diabetes had a two-fold increased
risk of all-cause mortality equivalent to loss of 9
years of life.
In this study in patients with a mean age of
51.5 years, with 3.1% previously diagnosed
with diabetes and 2.8% detected by screening,
mortality increased due to ischaemic heart dis-
ease (relative risk [RR], 2.40), stroke (RR, 1.98),
chronic liver disease (RR, 2.32), infections (RR,
2.29), liver cancer (RR, 1.54), pancreatic cancer
(RR, 1.84) and breast cancer (RR, 1.84). [JAMA
2017;317:280–289]
“This study is by far the largest prospective
study of adults with diabetes in rural and urban
China, demonstrating that diabetes is signifi-
cantly associated with increased mortality from
a wide range of diseases,” the authors stated.
“The study also highlights that the main
causes of death associated with diabetes dif-
fered between China and Western countries. In
China, diabetes is associated with more deaths
from stroke than ischaemic heart disease
whereas in Western countries, the opposite is
true,” they added.
Although the prevalence of diabetes was
1-15 APRIL 2017 • M A L AYS I A F O C U S • 18
higher in urban vs rural areas (8 vs 4%), mortal-
ity from chronic kidney disease (CKD; RR, 18.7
vs 6.8%) or diabetic ketoacidosis (RR, 115.3 vs
47.3%) was higher in patients from rural vs ur-
ban areas. [JAMA 2017;317:264–266]
Deaths from these diabetic complications,
particularly in rural areas, were much higher
than those reported in high-income countries.
For instance, mortality from CKD was about
four times higher in China as compared with the
US, Australasia, Japan, Korea and Singapore.
Deaths from diabetes-related CKD in China
have more than doubled since the 1990s. [Dia-
betes Care 2012;35:1835–1844; Diabetes Care
2003;26:360–366; Lancet 2016;387:251–272]
“These complications are highly indicative
of poor clinical management, especially in rural
areas, and significant weakness in the effec-
tiveness of prevention measures in the general
population,” commented Dr. Margaret Chan of
the WHO, who was not involved in the study.
[JAMA 2017;317:264–266]

“These problems are exacerbated by a se-
vere shortage of family physicians and lack of
quality primary healthcare services in both ur-
ban and rural areas,” she added. “This study
provides confidence in the Chinese govern-
ment to continue to propel health reforms to-
wards the right direction, with consequent im-
provement in the prevention and management
of diabetes.”
High red meat consumption may
increase arachidonic acid plasma
concentrations
AUDREY ABELLA
H igh red meat intake was significantly asso-
ciated with higher circulating arachidonic
acid (AA) plasma concentrations, a Singapore
study found.
Using data gathered from the Singapore
Prospective Study Program (SP2, n=269) and
the Singapore Chinese Health Study (SCHS,
n=769), researchers assessed habitual food
consumption relative to plasma concentra-
tions of AA and other polyunsaturated fatty
acids (PUFAs). [Nutrients 2017;doi:10.3390/
nu9020101]
The SP2 cohort was subdivided into three
categories based on intake ie, low fish, low
red meat (n=86); high fish (n=89); and high
1-15 APRIL 2017 • M A L AYS I A F O C U S • 19
The prevalence of diabetes among adults
had increased threefold between the 1980s
and 1990s. More recent findings estimated the
prevalence of diabetes among Chinese adults
to be 11.6% in 2013. Rapid economic growth,
industrialization and lifestyle changes are pos-
tulated as the main culprits for this expanding
epidemic. [Diabetes Care 1997;20:1664–1669;
JAMA 2013;310:948–959]
red meat (n=94). After adjusting for dietary
variables and lifestyle factors, the highest AA
concentration was found in the group consum-
ing high amounts of red meat (mean, 6.84;
p<0.001).
Among all the PUFAs in meat/meat alterna-
tives examined in the SCHS cohort, plasma AA
concentration was significantly higher with in-
creased red meat intake after adjusting for sex
and age (standard error [SE], 0.428 (0.018);
p<0.01) and dietary variables and lifestyle fac-
tors (SE, 0.500 (0.155); p<0.01).
“Our results suggest that dietary intake of
preformed long-chain fatty acids from … red
meat (for AA) are key determinants of plasma
concentrations of these fatty acids,” said the
researchers.

“A high intake of n − 6 PUFA or n − 6/n − 3
ratio has been postulated to increase inflam-
mation and cardiovascular disease (CVD) risk
… Our findings suggest that a diet with higher
amounts of fish, soy products and polyunsatu-
rated oil, along with lower amounts of red meat
might be optimal to achieve a plasma polyun-
saturated fatty acids profile that has been as-
sociated with lower inflammation and risk of
CVD,” said the researchers.
The researchers acknowledged that chang-
es in blood fatty acid concentrations due to diet
changes may have weakened their study obser-
Antimicrobial-coated screws tied to
less necrosis
STEPHEN PADILLA
T itanium surgical screws coated with polyvi-
nylpyrrolidone-polyurethane interpolymer
are associated with less necrosis than standard
uncoated screws, according to a Singapore
study. The coated screws also do not have cy-
totoxic side effects.
However, the authors noted that less necro-
sis does not mean reduced infection.
“Although techniques in orthopaedic sur-
gery are continually improving, the risk of in-
fection associated with orthopaedic surgery re-
mains a problem,” researchers said. “Infections
involving implants are particularly challenging
1-15 APRIL 2017 • M A L AYS I A F O C U S • 20
vations. Residual confounders, measurement
error due to self-reporting, cross-sectional de-
sign and ethnicity of the study population also
limited their findings, they said.
to treat and are associated with high morbidity
rates and high monetary costs.”
To determine whether antimicrobial-coated
screws would not be toxic to the bone and that
the likelihood of infection would be reduced, ti-
tanium screws were inserted into the left supra-
condylar femoral regions of 16 rabbits.
The screws were either coated with a polyvi-
nylpyrrolidone-polyurethane interpolymer with
tertiary amine functional groups (experimental
group; n=8) or uncoated (control group; n=8).
It has been shown that polyvinylpyrrolidone-
polyurethane interpolymer prevents bacterial
adhesion, according to researchers.
“When the coating is exposed to bodily flu-

ids, bacteria are destroyed by the electrostatic
interaction between the cationic coating and
the anionic bacterial outer membrane. This
interaction increases the permeability of the
bacterial outer membrane, damaging the mem-
brane and killing the bacteria,” they said.
Histological samples were collected and ex-
amined at week 6. The presence of necrosis, fi-
brosis and inflammation in the bony tissue and
the tissue surrounding the screws were then
recorded.
There was no external sign of infection seen
in any rabbit, and none of the cultures grew
bacteria. All the rabbits from the experimental
group had live, cellular bone marrow, but this
was replaced with connective tissue in four rab-
bits from the control group. [Singapore Med J
2017;58:46-49]
All eight rabbits from the control group had
necrosis in fatty bone marrow, which presented
in only two rabbits from the experimental group.
Inflammation was observed in five rabbits from
1-15 APRIL 2017 • M A L AYS I A F O C U S • 21
the control group and in only one rabbit from
the experimental group.
“Implants are essential for joint replacement
and fracture fixation,” researchers said. “How-
ever, even when all precautions are taken, im-
plant infection rates range from 1 to 2 percent,
with higher infection rates reported for internal
and external fracture fixations.”
Concerns regarding bacterial mutation, ad-
aptation and resistance to antibiotics were ir-
relevant since the antimicrobial coating used in
this study was not antibiotics. The coating used
in the trial covered the surface of the screw and
protected it from contact with bodily fluids. With
neither an absorbable nor a soluble coating,
bacterial growth was stopped.
The absence of a chronic toxicity assess-
ment was the major limitation of the study,
according to researchers, adding that further
studies are needed on polyvinylpyrrolidone-
polyurethane interpolymer-coated screws and
the effect of using these screws.

Stigma negatively impacts
adherence to psychosis treatment
JACKEY SUEN
S tigma negatively impacts treatment adher-
ence among patients with psychosis in
Hong Kong, a recent survey has shown.
Among 300 patients with psychotic disor-
ders who responded to the survey, 30% admit-
ted lying about the reason for taking antipsy-
chotic medications, while 19% felt ashamed of
taking antipsychotics.
“Surprisingly, the stigma towards antipsy-
chotic treatment existed even among a signifi-
cant proportion of respondents with a high level
of insight about their disease,” reported Profes-
sor Eric Chen, of the Department of Psychiatry,
The University of Hong Kong, who is chairman
of the Early Psychosis Foundation.
“Forty percent of the respondents were non-
adherent to their medications. Another 40% ex-
pressed concerns about disclosing their illness
and treatment,” he continued.
The survey, conducted by the Early Psy-
chosis Foundation between June and October
2016 in patients with psychotic disorders from
Queen Mary Hospital, Baptist Oi Kwan Social
Service, Alliance of Ex-mentally Ill of Hong Kong
and New Life Psychiatric Rehabilitation Associ-
ation, also established an association between
medication nonadherence and stigma. Signifi-
cantly more respondents who did not adhere
to antipsychotics believed that people on anti-
psychotics are useless and dangerous (17% vs
1-15 APRIL 2017 • R E G I O N A L • 23
Professor Eric Chen (middle), Nicole Lau (right)
8–9% in patients who adhered to antipsychot-
ics).
“Clinicians have attributed the high medica-
tion nonadherence rate of psychosis patients
to lack of knowledge and insight about the dis-
ease,” noted Chen. “However, the correspond-
ing psychoeducation approach has achieved
only limited success in improving adherence as
it focuses on brain abnormality, which is con-
sidered unchangeable and aggravates stigma.
It fails to acknowledge the effect of stigmati-
zation as a factor behind its ineffectiveness in
improving patients’ attitude and behaviour to-
wards treatment.”
In the survey, patients with high levels of
brain and mind attributions of psychosis were
found to have more positive attitudes towards
antipsychotic treatment and medical profes-
sionals, while positive attitudes in the patients’
close social circles were helpful in reducing
stigma and improving treatment adherence.
“A three-pronged approach is needed to

help patients understand the brain and mind
attributions of the disease, guide them to ap-
preciate the interaction between the two, and
encourage support from their families and part-
ners. This can assist patients in building a posi-
tive attitude towards antipsychotic treatment
and effectively support their recovery,” he sug-
gested.
“In response to the survey’s findings, the
Early Psychosis Foundation will launch the iPAT
project to encourage communication between
Colistin resistance gene mcr-
1 found in wide variety of E. coli
strains in China
CHRISTINA LAU
T he mcr-1 gene, which confers transferable
colistin resistance, has been found in a
wide variety of Escherichia coli strains isolated
from human samples in China following recent
report of its prevalence in raw meat and food
animals in the country.
The new study on mcr-1–positive Enterobac-
teriaceae (MCRPE) in China showed substan-
tial horizontal dissemination of mcr-1 through
E. coli populations, with previous carbapenem
use identified as a risk factor. [Lancet Infect
Dis 2017, doi: http://dx.doi.org/10.1016/S1473-
3099(16)30527-8]
1-15 APRIL 2017 • R E G I O N A L • 24
patients and their families about the illness and
its treatment. This will help strengthen mutual
support between patients and their families,
thereby eliminating self-stigmatization,” ex-
plained Nicole Lau, senior project manager of
the Early Psychosis Foundation. “In the project,
a series of promotional activities will be rolled
out to educate patients on assessing their
status of recovery, and to raise their aware-
ness of the interaction between the brain and
the mind.”
In the study, researchers retrospectively
assessed the prevalence and risk factors of
MCRPE infection using isolates of Gram-neg-
ative bacteria collected in 2007–2015 at two
tertiary care hospitals in Zhejiang and Guang-
dong, which served a catchment population
of 9 million and 13.5 million, respectively. Risk
factors for mcr-1–positive E. coli carriage were
prospectively assessed using rectal swabs col-
lected at the hospitals and from healthy volun-
teers.
Among 17,498 isolates associated with in-
fection, mcr-1 was detected in 76 (1%) of 5,332
E. coli isolates, 13 (<1%) of 3,480 Klebsiella
pneumoniae isolates, one (<1%) of 890 En-

terobacter cloacae isolates, and one (1%) of
162 Enterobacter aerogenes isolates.
In rectal swabs collected from inpatients
(n=1,200) and healthy volunteers (n=2,923),
mcr-1 was found in 35 (3%) of 1,199 E. coli iso-
lates from inpatients, one of one E. cloacae iso-
late from inpatients, and 19 (1%) of 2,923 E. coli
isolates from healthy volunteers.
Among all 146 MCRPE isolates identified,
five E. coli isolates from clinical samples were
also resistant to carbapenems.
“Multi-locus sequence typing [MLST] analy-
sis showed extreme divergence of E. coli strains
carrying mcr-1 not only between Zhejiang and
Guangdong, but also within each hospital,” the
researchers reported. “mcr-1 was found in 30
[26%] of 116 ST clades from Guangdong, in-
cluding ST131, and 25 [34%] of 73 ST clades
from Zhejiang. Seventeen mcr-1–positive E.
coli isolates belonged to new or unreported
MLST groups.”
Risk factors for mcr-1–positive E. coli infec-
tion were male gender (63% vs 41% for mcr-
1–negative E. coli; adjusted p=0.011), immu-
nosuppression (15 vs 6%; adjusted p=0.011),
and antibiotic use in the previous 3 months,
particularly carbapenems (24 vs 9%; adjusted
p=0.002) and fluoroquinolones (30 vs 19%; ad-
justed p=0.017).
“Emergence of mcr-1 heralds the breach of
antibiotics of last resort. Withdrawal of colistin
from agricultural use and its subsequent clini-
cal use in China may reduce colistin resistance
rates in the community and increase resistance
rates in hospitals. The significant risk factors for
mcr-1–positive E. coli infection are likely to be
1-15 APRIL 2017 • R E G I O N A L • 25
exacerbated when colistin is used clinically,”
the researchers wrote.
In another study of 2,066 isolates collected
from patients with bloodstream infections at
28 hospitals in China, 20 (1%) of 1,495 E. coli
isolates and one (<1%) of 571 K. pneumoniae
isolates were mcr-1–positive. All mcr-1–positive
isolates were susceptible to tigecycline, while
95% were susceptible to the carbapenem/β-
lactamase combination of piperacillin plus
tazobactam. One mcr-1–positive E. coli iso-
late also produced NDM-5, which confers re-
sistance to β-lactam antibiotics. [Lancet Infect
Dis 2017, doi: http://dx.doi.org/10.1016/S1473-
3099(16)30528-X]
“At this stage, we can conclude that the
doomsday scenario of convergence of car-
bapenem resistance and colistin resistance
(via mcr-1) has not yet occurred to any great
extent in China. The spread of mcr-1 into glob-
ally widespread and virulent strains such as
ST131 is cause for concern and surveillance,”
wrote editorialists in a linked comment. [Lancet
Infect Dis 2017, doi: http://dx.doi.org/10.1016/
S1473-3099(17)30053-1]
“After carbapenems, new antibiotics will be-

come available for clinical use in China. There
are risks that low-cost generic copies of these
new antibiotics will be used in agriculture. We
must be vigilant to this possibility and urge Chi-
nese authorities to proactively prohibit use of
1-15 APRIL 2017 • R E G I O N A L • 26
these crucial antibiotics outside of appropri-
ate use in human beings. Without such inter-
ventions, there will doubtless be more serious
problems than mcr-1 in China in the near fu-
ture,” they concluded.

New treatment for pulmonary
embolism introduced in Hong Kong
JACKEY SUEN
A new ultrasound-accelerated thrombolysis
treatment for pulmonary embolism was
successfully applied for the first time at two
public hospitals in Hong Kong.
“Our patient was clinically stabilized after
treatment with the EkoSonic Endovascular
System [EKOS], reporting no desaturation or
shortness of breath. The patient’s blood pres-
sure also normalized,” reported Dr. Wing-Hang
Luk, consultant radiologist at the Princess Mar-
garet Hospital, who performed the first case of
pulmonary embolism treatment with EKOS in
Hong Kong.
“The EKOS system enables much lower dos-
es of thrombolytic drugs to be used in patients
with pulmonary embolism. This significantly re-
duces the risk of major bleeding,” noted Pro-
fessor Bryan Yan, of the Division of Cardiology,
Chinese University of Hong Kong, who treated
the second patient with submassive pulmonary
embolism with the EKOS system. “The system
is currently the only US FDA-approved minimal-
ly invasive endovascular therapy for pulmonary
embolism.”
“Our patient’s condition improved signifi-
cantly after 12 hours of ultrasound-assisted
thrombolysis with the EKOS system,” reported
Yan. “His breathing and blood pressure im-
proved, while his grossly dilated right heart was
restored to nearly normal size. The patient was
1-15 APRIL 2017 • R E G I O N A L • 27
subsequently discharged.”
The EKOS system is applied with thrombo-
lytic drugs to dissolve blood clots, restore nor-
mal function of the heart and normalize blood
flow in patients with pulmonary embolism.
Blood clots are tightly bound together by fi-
brin. This structure blocks thrombolytic drugs
from reaching the site of action, necessitating
a higher drug dose for effective thrombolysis.
The EKOS system emits acoustic pulses to
unwind fibrin, thus allowing more thrombolytic
drugs to reach deeper into the clot and hence
reducing the dose required to achieve throm-
bolysis. [Pathology 1997;29:263–266; Circula-
tion 2014;129:479–486]
The EKOS system was shown in studies to
accelerate time to clot dissolution, increase
clot removal and enhance clinical improvement
compared with standard catheter-directed drug
therapy or thrombectomy. These improvements
led to reductions in treatment duration and
thrombolytic drug use, and hence the risk of

treatment-related complications and bleeding.
[Vascular 2009;17(Suppl 3):S137–S147; Per-
spect Vasc Surg Endovasc Ther 2010;22:152–
163; Circulation 2014;129:479–486; JACC Car-
diovasc Interv 2015;8:1382–1392]
“The prevalence rate of fatal pulmonary em-
bolism in Hong Kong had increased from 0.21%
in 1964–1974 to 1.08% in 1975–1979, 1.83% in
1980–1984, 2.77% in 1985–1990 and 4.7% in
1990–1994,” added Luk. “The rate has contin-
Most Chinese patients accept
chaperones in intimate physical
examinations
DR. JOSEPH DELANO FULE ROBLES
A recently published study reports that over
90% of respondents in Hong Kong consid-
ered the presence of a chaperone during an in-
timate physical examination (IPE) appropriate.
Eighty-four percent of the respondents also felt
that doctors should request for a chaperone.
The cross-sectional survey included 150
patients at a public teaching hospital in Hong
Kong, 55% of which were from the Accident and
Emergency Department and 45% from the sur-
gical outpatient clinic. Results showed that 50%
of female respondents prefer a female doctor to
perform IPE, while 75% of female respondents
also said a chaperone is necessary if a male
1-15 APRIL 2017 • R E G I O N A L • 28
Dr. Wing-Hang Luk Professor Bryan Yan
ued to increase in recent years, approaching
that in Western countries.”
doctor is doing the examination. [Hong Kong
Med J 2016, doi: 10.12809/hkmj164899]
For male respondents, the majority do not
have a preference for the gender of the doctor
performing IPE (64%) or whether a chaperone
is present at the time of examination (52%).
“The findings of our study are similar to the
situation in the UK and Australia, where pa-
tients are aware of and prefer this practice,” the
authors said.
“Our findings suggest a high degree of ac-
ceptance in Hong Kong for the presence of a
medical chaperone during IPEs,” they added.
Seventy-seven percent of respondents re-
ported previous experience with IPEs. For
those who had previous IPEs without chaper-
 1-15 APRIL 2017 • R E G I O N A L • 29

ones, 75% of women and 44% of men said they

would prefer to have a medical chaperone.
Most respondents (72%) consider health-
care workers as suitable chaperones. Some
would deem a family member (53%) or a friend
(20%) appropriate.
According to the respondents, the most com-
mon reasons for preferring chaperones during
IPEs are to have an objective account should
legal issues arise (61%), to protect themselves
from sexual harassment (48%), and for psycho-
logical support (43%). “One limitation of our study is that the num-
Significantly more men (44%) than women ber of participants was small and the results
(27%) prefer not to have a chaperone because may not readily be generalizable, particularly
they consider the presence of a chaperone em- outside the public hospital setting, where pa-
barrassing (34%; p=0.003) and undermining tients are likely to be more familiar with their
their privacy (26%). doctors and have more control over which doc-
IPE in this study is defined as breast, pel- tor examines them,” the authors mentioned.
vic and/or per-rectal examination. In addition to “Our cohort also consisted of relatively
these, more women than men consider chest young patients [<30 years old; 15%], which
examination of the respiratory system to be in- may affect the ability to demonstrate any im-
timate (44 vs 14%; p<0.01). pact of age,” they added.
Bacillus clausii spores:
Sponsored Clinical Summary

Assured viability for the

effective treatment of diarrhoea
Probiotics have a long history of use in humans. Defined as "live organisms that confer a health benefit on the
host when administered in adequate amounts", the spectrum of use of probiotics in humans ranges from foods
and dietary supplements to pharmaceutical/nutraceutical products to affect general health and disease. While the
genera Lactobacillus and Bifidobacterium are the two most common probiotics associated with consumer products,
there exist other organisms (eg, the yeast Saccharomyces cerevisiae, some non-pathogenic strains of Escherichia coli
and Bacillus species) that are used as probiotics.1–3 One of them is the probiotic strain B. clausii that has been found
to be effective for the treatment of diarrhoea and antibiotic-associated gastrointestinal side effects.4–6

Key factors contributing to Bacillus
spore resistance
Bacteria belonging to the Bacillus genus, including
B. clausii, are known to form spores, ie, dormant life
forms of the bacteria that can exist in the dehydrated
state indefinitely. Sporulation is usually triggered when
there is low level of nutrients in the environment. The
dormant cell produced by this process has no detectable
metabolism and demonstrates a high degree of resistance
to adverse conditions such as wet and dry heat, ultraviolet
and gamma radiation, extreme desiccation (including
vacuum) and oxidizing agents.7,8
Laboratory studies that evaluated spore resistance in spore-
forming bacteria have found that the following factors are
important for the level of spore resistance.8
Genes. Certainly, genetic make-up of the organism has
 exert their effect through indirect modulation on spore
a role where it has been shown that spores of bacterial
species that thrive at relatively high temperatures
(thermophiles) are more resistant to wet heat compared
with those that thrive under moderate (mesophiles) or
cold temperatures (psychrophiles).
Sporulation condition. Sporulation that occurs at elevated
 It also appears that α/β-type SASP have a role in
temperatures typically produces spores that are more
heat resistant, partly due to a decrease in core water
content in the spores.
Spore coat. Spore coat confers resistant properties by
 expression of α/β-type SASP as a result of gene deletion
being unyielding to enzymatic lysis and the action of
certain chemicals such as hydrogen peroxide.
Core impermeability. The spore core is relatively

impermeable to hydrophilic molecules greater than
approximately 200 kDA, possibly due to presence of
membranes that act as a permeability barrier.
Core water content. The core of the spore has a lower
 in determining spore resistance to dry heat is DNA repair
water content compared with the outer layers and there is
ample evidence to show that this lowered water content
is inversely related to heat resistant properties.
Spore mineral content. In general, spores containing
 Other factors that are protective against dry heat
divalent cations are more resistant than those with
monovalent cations. These cations are usually confined
to the spore core. An increase in core mineralization is
often associated with decreased core water content that
could lead to increased resistance to wet heat.
α/β-type small, acid-soluble proteins (SASP). During
 multiple cycles of freeze-drying at extreme temperatures.
sporulation, spore DNA forms complexes with a group
of specialized proteins, ie, α/β-type SASP that not only
Bacillus spores are resistant to extreme
heat environment
The current understanding of the various factors
contributing to Bacillus spore resistance to extreme heat
environment is facilitated by laboratory studies using
Bacillus subtilis as well as other spore-forming bacteria.8
Wet-heat resistance.8 Bacillus spores are known to be
resistant to wet heat as they require incubation temperature
of 30 to 40oC higher than that needed by growing Bacillus
cells to be inactivated. Factors that are crucial to the spore
resistance to wet heat include sporulation temperature,
protection of spore DNA by α/β-type SASP, spore core
mineralization and spore core dehydration. Spore core
water content is the major factor in determining wet-heat
resistance and among the factors listed, two of them, ie,
sporulation temperature and spore core mineralization
core water. It is suggested that reduced water content in
the core reduces the amount of water associated with spore
proteins, hence providing a stabilization effect against wet-
heat denaturation.
protecting spores from DNA damage by wet heat. While
it is generally accepted that spore killing by wet heat does
not occur through DNA damage such as depurination,
studies have shown that mutant B. subtilis lacking the
were more sensitive to wet heat. The mechanism of spore
killing was largely attributable to DNA damage, including
formation of abasic sites presumably due to depurination.
Dry-heat resistance.8 Dry heat has a direct effect on spore
killing because spores exposed to dry heat acquire both DNA
damage and mutation. An important factor that is crucial
mechanism. Spores with mutant DNA repair mechanism
are susceptible to dry heat and upon germination, genes
encoding for DNA repair proteins are also greatly induced.
include spore core mineralization and DNA protection by
α/β-type SASP.
Desiccation resistance.8 Compared with vegetative cells,
Bacillus spores are more resistant to desiccation and
When rehydrated following the treatment, wild-type
spores often show no detectable killing and the key reason
simulated laboratory conditions, extreme heating (ie,
at temperatures exceeding those normally prevailing in
most environment on the Earth’s surface) for an extended
period resulted in little or no detectable loss in Bacillus
spore viability.
Mode of action of B. clausii spores in
exerting its antidiarrhoeal effect
B. clausii spores are thought to exert their antidiarrhoeal
effect by normalizing intestinal flora composition. Upon
ingestion, spores of B. clausii appear to adhere to the
epithelial cells of the upper intestinal tract where the
environment (higher oxygen level, rich in nutrients) is
conducive for the spores to germinate into vegetative
cells.7,9 In its vegetative form, B. clausii produces a myriad
of antibiotic and antimicrobial compounds as well as
extracellular enzymes that are relevant to its mode of
action.7 B. clausii also has immunomodulatory effects by
inducing nitric oxide synthase (NOS) II activity, interferon-γ
production and CD4+ T-cell proliferation.10
Pharmaceutical stability of B. clausii
spores ensures assured viability
As highlighted earlier, spores are metabolically dormant life
forms that are extremely resistant to adverse conditions. In
oral bacteriotherapy, this feature is particularly useful as it
allows for the formulation of stable pharmaceutical products
where no specific storage condition is required. B. clausii
spores can be maintained at room temperature for several
years as a water suspension, without loss of cell titre.7
Summary
Diarhoeal disease continues to afflict a significant
proportion of the global population.11 The condition is
treatable and in recent years, pharmaceutical probiotics
have found a role in the treatment of diarrhoea and
antibiotic-associated side effects. One of them is
B. clausii spores, the metabolically dormant life form of
B. clausii that are resistant to extreme thermal conditions.
This unique feature allows for the formulation of a stable
pharmaceutical product, thus providing assured viability
for the effective treatment of diarrhoea.
Abbreviated Prescribing Information: 1. TRADE NAME OF THE MEDICINAL PRODUCT
AND PRESENTATION: Enterogermina 2 Billions /5 ml oral suspension. Each 5 ml contains
spores of poly-antibiotic resistant Bacillus clausii 2 billion. 2. THERAPEUTIC INDICATION:
Treatment and prophylaxis of intestinal dysmicrobism and subsequent endogenous
dysvitaminosis. Therapy for aiding the recovery of the intestinal microbial flora, altered
during the course of treatment with antibiotics or chemotherapeutic agents. Acute and
chronic gastrointestinal disorders in breastfeeding infants, attributable to intoxication or
intestinal dysmicrobism and dysvitaminosis. 3. DOSAGE AND INSTRUCTIONS FOR USE:
Adults: 2-3 minibottles per day; children: 1-2 minibottles per day; breastfeeding infants:
1-2 minibottles per day. Minibottles: administration at regular intervals (3-4 hours), taking
the contents of the minibottles as it is or diluting it in water or other drink (e.g. milk, tea,
orange juice). 4. CONTRAINDICATIONS: Known hypersensitivity to any of its ingredients.

change the structure and properties of the DNA but also
reduce the DNA’s reactivity to damaging chemicals. As
a consequence, the genetic material of the spores is not
behind this resistance is DNA protection by α/β-type SASP.
Indeed, mutant spores devoid of this protective protein are
more susceptible to extreme freeze-drying or desiccation
5. SPECIAL WARNINGS AND PRECAUTIONS: This medicine is for ORAL use only. DO
NOT inject or administer in any other way. Possible presence of corpuscles visible in the
minibottles due to aggregates of Bacillus clausii spores and therefore shake the minibottle
before use. During antibiotic therapy, the product should be administered in the interval
between one dose of antibiotic and the next. 6. PREGNANCY AND LACTATION: There

damaged by heat or genotoxic/mutagenic chemicals.
DNA or protein repair mechanisms. Finally, the existence
 desiccation (10-6 Pa at 77 K for 24 hours).
of DNA repair mechanisms in the form of enzymes
and various heat shock proteins appear to confer spore
resistance. Upon germination, these proteins are activated
to repair DNA or protein damage and might have a role in
determining spore survival after various treatments.
and demonstrate DNA damage. One study reported that
the survival rate of B. subtilis was 75% following extreme
Resistance to solar heating.8 Sunlight drives all living
processes on Earth. However, it is also an important
source of lethal damage to spore cellular component and
DNA. Heating is an indirect effect of solar radiation; under
are no contraindications regarding the use of the product during pregnancy and while
breast-feeding. 7. UNDESIRABLE EFFECTS: Rash and urticaria have been reported.
8. INTERACTIONS: Not known. 9. OVERDOSE: Not known. Ref No.: Entero/Vo1/1015.
References: 1. World Gastroenterology Organisation Global Guidelines. Probiotics and prebiotics, October 2011. Available at: http://
www.worldgastroenterology.org/UserFiles/file/guidelines/probiotics-english-2011.pdf. Accessed 13 February 2017. 2. Moslehi-
Jenabian S, et al. Nutrients 2010;2:449–473. 3. Behnsen J, et al. Cold Spring Harb Perspect Med 2013;3:a010074. 4. Lahiri K, et al.
J Dent Med Sci 2015;14:74–76. 5. Arzese A, et al. Mom Med Chir 2001;2 (suppl 1):2–8. 6. Nista EC, et al. Aliment Pharmacol Ther
2004;20:1181–1188. 7. Mazza P, et al. Boll Chim Farm 1994;133:3–18. 8. Nicholson WL, et al. Microbiol Mol Biol Rev 2000;64:548–
572. 9. Hong HA, et al. FEMS Microbiol Rev 2005;29:813–835. 10. Urdaci MC, et al. J Clin Gastroenterol 2004;38(6 Suppl):S86–S90.
11. World Health Organization. Diarrhoeal disease. Fact sheet No. 330, April 2013. Available at: http://www.who.int/mediacentre/
factsheets/fs330/en/. Accessed 13 February 2017.

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Low survival rate of out-of-hospital
cardiac arrests in HK
CHRISTINA LAU
T he first territory-wide study on out-of-hos-
pital cardiac arrests in Hong Kong reports
a high incidence and a low survival rate com-
pared with global data.
Among 5,154 cases of out-of-hospital cardi-
ac arrests attended by the emergency medical
service of the Hong Kong Fire Services Depart-
ment between 1 August 2012 and 31 July 2013,
only 2.3 percent of patients (n=121) were alive
at 30 days or survived to hospital discharge.
[Hong Kong Med J 2017, doi: 10.12809/
hkmj166046]
“The incidence of 72 arrests per 100,000
person-years [reported in this study] is high-
er than the global average of 55 per 100,000
person-years,” the authors noted. “The survival
rate of 2.3% in Hong Kong is low compared with
Western countries. It is also at the lower range
of survival rate among major Asian cities.”
Of note, ventricular fibrillation or ventricular
tachycardia was identified as initial rhythm in
only 8.7% of patients. According to the authors,
this could be an explanation for the low surviv-
al rate, in addition to the high median age (80
years) of the patients.
A majority of out-of-hospital cardiac arrests
occurred at the patient’s home (51.7%) or home
for the aged (30.4%). Approximately 60% of the
arrests were unwitnessed.
Bystander cardiopulmonary resuscitation
1-15 APRIL 2017 • R E G I O N A L • 31
(CPR) and automated external defibrillation
(AED) were performed in 28.8 and 1.4 percent
of cases, respectively. “Although the bystand-
er CPR rate in this study almost doubled from
15.6% in 1999, there is still room for improve-
ment. Furthermore, the rate of defibrillation by
bystanders was very low,” the authors noted.
“The low rate of ventricular fibrillation or
ventricular tachycardia [as initial rhythm] may
be influenced by the low bystander CPR rate
and the high proportion of unwitnessed cases,”
they suggested. “Targeted measures, such as
implementation of a territory-wide public ac-
cess defibrillation programme and community-
based CPR education and training, are needed
to improve the chances of survival following
out-of-hospital cardiac arrests.”
Among the 5,154 cases analyzed, the me-
dian response time of the emergency medical
service was 9 minutes, which is in the mid-
range compared with major Asian cities. “How-
ever, the median time to first defibrillation of 12

minutes is long,” the authors noted.
The location of arrest, initial ECG rhythm,
and time from call to first defibrillation were
found to be independent predictors of survival
at 30 days. Among the 121 survivors, 78 pa-
tients (1.5% of overall study population) had
good neurological outcome (cerebral perfor-
mance category score ≤2) on discharge from
hospital.
1-15 APRIL 2017 • R E G I O N A L • 32
The study, conducted by The University of
Hong Kong, The University of Hong Kong–
Shenzhen Hospital and North District Hospital,
was a retrospective analysis of prospectively
collected data of the emergency medical ser-
vice’s out-of-hospital cardiac arrest database.
Limitations included the analysis of data col-
lected for 12 months only and the lack of data
on post-resuscitation care.
ASIAN PACIFIC
DIGESTIVE WEEK
23 – 26 SEP TEMBER 20 1 7
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THE FUTURE IN DIGESTIVE DISEASES

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Depression tied to increased
risk of neurocognitive
disorders in Chinese elderly
PEARL TOH
D epression is associated with an increased
risk of mild neurocognitive disorders
(NCD) in Chinese elderly, according to data
from the Singapore Longitudinal Ageing Study
(SLAS) cohort.
The prospective study followed 889 commu-
nity-dwelling Chinese elderly (age ≥55 years)
in the SLAS cohort who were cognitively normal
at baseline, as determined by the Mini-Mental
State Examination (MMSE). [J Nutr Health Ag-
ing 2017;21:161–164]
After a mean follow-up duration of 45 months
(range, 10 to 62 months), 59 incident mild NCD
cases were identified (cumulative incident rate,
6.6%). A higher proportion of those with inci-
dent NCD cases had depression at baseline
compared with those still maintaining normal
cognition (18.6% vs 9.8%; p=0.03).
Compared with participants without depres-
sion at baseline, those who were depressed
had higher incidence of mild NCD (6.0% vs
12.0%) at follow-up. Indeed, participants with
depression were more than twice as likely as
those without depression to develop mild NCD
at follow-up (adjusted odds ratio [OR], 2.56;
p=0.019), after adjusting for age, sex, hyper-
tension, heart disease, diabetes mellitus, apo-
lipoprotein E (APOE) genotype, education sta-
1-15 APRIL 2017 • R E G I O N A L • 34
Loneliness in older adults tied to less healthcare utiliza-
tion
tus, and length of follow-up.
“This effect size is considerable taking into
the fact that in our study sample, the OR of
mild NCD for age (in years) was 1.08, mean-
ing 8% extra risk for each year [of] increase in
age,” according to the researchers led by Dr.
Lei Feng, of the Department of Psychological
Medicine at Yong Loo Lin School of Medicine in
the National University of Singapore.
In addition, incident NCD cases were more
likely to be older (68.2 vs 64.1 years; p=0.001),
have lower education level (primary level and
below, 61.0% vs 41.2%; p=0.003), and lower
cognitive score at baseline based on MMSE
(28.1 vs 28.5; p=0.02).
There was no evidence of APOE genotype
modifying the association between depression
and mild NCD (p interaction=0.263).
As MMSE is a screening tool, it may not be

sensitive enough to detect subtle cognitive
decline in elderly without dementia, noted the
researchers, who said pre-existing subtle cog-
nitive impairment that had been undetected
might have reversely contributed to depressive
symptoms.
Nonetheless, they acknowledged that “the
findings are particularly important as depres-
sion is still viewed with stigma in many Asian
societies, especially among the elderly.”
1-15 APRIL 2017 • R E G I O N A L • 35
“Our results highlight the need to consider
the cognitive sequelae of depression and how
depression can be a potentially modifiable risk
factor of cognitive decline,” said the research-
ers. “If indeed depression was to be confirmed
as a treatable cause for NCD, we could expect
a dramatic impact at the public health level in
terms of reduced NCD incidence among de-
pressed older persons after adequate interven-
tion.”
 Multidisciplinary Musculoskeletal Ultrasound Congress
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Dr. James Linklater (Australia)
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Dr. Tai-pang Ip (Hong Kong) Dr. Carrel Yu (Hong Kong)
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Dr. Sheung-wai Law (Hong Kong)
Many more distinguished speakers to follow…

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Enquiry
Congress Secretariat
MIMS (Hong Kong) Limited Early-bird Registration Deadline 10 April 2017
Tel: (852) 2155 8557 or 2116 4348
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 Sponsored Symposium Highlights

Vortioxetine and the one-year

experience in Malaysia
Depression is a complex but common mental illness in Malaysia.1 Treatment for depression has been traditionally focused on improving
mood symptoms; however, some patients still experience residual symptoms, such as sleep and memory problems, as well as difficulty in
concentrating and planning, although in remission (ie, having a MADRS score of below 10).

On 6 November 2016, in conjunction with the first year anniversary of vortioxetine (Brintellix®, Lundbeck) in Malaysia, two distinguished
speakers, Professor Gin S Malhi and Dr Pranab Kalita shared updates on depression and the use of vortioxetine in order to help patients with
major depressive disorders (MDD) to return to their premorbid functional states. The session was followed by three case presentations.

ReCognizing Depression and Redefining Functional Outcomes

Professor Gin S Malhi
Executive and Clinical Director
Clinical Assessment Diagnostic Evaluation (CADE) Clinic
Royal North Shore Hospital & University of Sydney
Sydney
Depression is not limited to having a low mood, but
more importantly, involves functional impairment. Other
symptoms include guilt, anhedonia and cognitive symptoms,
such as psychomotor agitation/retardation, diminished
ability to think or concentrate, and indecisiveness, said
Professor Malhi.
Although the DSM-52 and ICD-103 have classified and
described the various types of mood disorders, these
definitions may not be very helpful as many symptoms
listed lack specificity, making them difficult to use in clinical
practice. In addition, patients seen in day-to-day clinical
practice have heterogeneity of symptoms despite having
the same diagnosis.
To provide a more holistic definition of depression, the
Royal Australian and New Zealand College of Psychiatrists
(RANZCP) has developed mood disorder clinical practice
guidelines, which can be used to manage individuals who
share certain features by specifying episodes of illness,
patient’s response to treatment and clinical features.4
Professor Malhi explained that there are several subtypes
of MDD, but the key distinction to be made is that between
single episodes and recurrent, persisting illness. These
subtypes are often difficult to distinguish from each other,
because most patients experiencing a single episode will
eventually encounter recurrent episodes in their lifetime.
Long-term management of such patients can be challenging,
because treatment will also depend on the pattern of their
depressive episodes.
Cognitive symptoms are common in Figure 1. Mapping of patients’ descriptors of
depression cognitive symptoms to cognitive domains
Cognitive symptoms or cognitive dysfunction – which
are described as having a diminished ability to think or ATTENTION MEMORY
concentrate, being indecisive, or having psychomotor Lose train of thought No short-term memory
agitation or retardation2,3 – are common in depression,5,6
and can greatly affect patients’ work functioning.7 As such, Not listening Attention
recognizing and treating these symptoms are important Forgetful
steps in managing MDD.4,8,9 Concentration
CONFUSED
Can’t calculate
A range of depression rating scales have been developed to Brain is Lack of INADEQUATE
assess cognitive dysfunction in patients, but these scales cloudy focus OVERWHELMED
are, at times, complicated to use and unable to assess all Can’t multi-task
cognitive domains. Therefore, Professor Malhi emphasized Slow motion
Lack of confidence
that when assessing a patient, the clinician should be
able to tailor simple diagnostic questions and interpret Tired / lethargic Procrastinate
Indecisive
the patient’s complaints by mapping them according to
the four cognitive domains shown in Figure 1. Objective PSYCHOMOTOR SPEED EXECUTIVE FUNCTION
and subjective measurements can also be used to gain
a clearer overview of cognitive function in the patient.
All patients should be regularly monitored for cognitive
do not respond at all to the chosen treatment, switching to
dysfunction during treatment and remission because
a different class of antidepressant may be needed because
cognitive dysfunction is found to persist in many patients
antidepressants of the same class would usually have a
even in remission.10
similar mechanism of action, explained Professor Malhi.
Individualizing treatment for optimum Key messages
● Cognitive dysfunction is a key symptom in MDD; it is
treatment outcomes important for clinicians to recognize cognitive complaints
A broad range of pharmacotherapy is available for made by patients during consultation.
depression. The most effective antidepressant is one that
● Treatment for depression should not only focus on
works best in a particular patient and that prevents chronicity
improvement in overall depressive symptoms, but
of symptoms. As such, clinicians play an important role
in determining the type of depression a patient has and also on the individual symptoms. Treatment should
subsequently, choosing an appropriate treatment. If the be individualized according to the patient’s profile for
patient does not respond or responds inadequately to optimum outcomes.
the treatment, clinicians should reassess the patient’s ● Regular monitoring of a patient’s response to treatment
condition and reformulate the treatment. For patients who is necessary to determine treatment efficacy.

ReCognizing the Efficacy and Safety of Vortioxetine

Dr Pranab Kalita
Medical Director, Medical Affairs
Lundbeck South East Asia
Depression is a disease with a heterogenous
presentation.11,12 Due to this reason, the rate of chronic
or recurrent depression remains high despite treatment.13
This suggests that there is still room for improvement in
depression management to fulfil patients’ expectations
from treatment, which include full recovery in functionality,
quality of life and cognition.14
Vortioxetine in MDD
Vortioxetine is an antidepressant approved in Malaysia
39.4% in the agomelatine group.22 The remission rates significantly better than placebo in improving the
achieved in this study are higher than those reported in composite z-score, which comprised of the DSST and
comparable patient groups investigated elsewhere.22,23
RAVLT scores, in adults with recurrent moderate-to-severe
MDD.26 Similarly, in the CONNECT study, vortioxetine,
● Elderly population with recurrent MDD but not duloxetine, was associated with improvements
Compared with placebo, vortioxetine 5 mg significantly in cognition and daily functioning, as measured by the
improved the symptoms of depression in elderly patients DSST (Figure 3) and UPSA, respectively.18 In the elderly
(aged above 65 years). At week 8 of treatment, there was
a 3.3-point reduction in the HAM-D24 total score with population with MDD, vortioxetine was also reported
to improve DSST, RAVLTacq and RAVLTdelay among
vortioxetine 5 mg versus placebo.24
these patients.24
● Depressed patients with high levels of anxiety
(HAM-A score ≥20)
A recent meta-analysis showed that 5, 10 and 20 mg Figure 3. CONNECT: Vortioxetine, but not
duloxetine, led to cognitive improvement as
vortioxetine was efficacious in reducing depressive and
anxiety symptoms in patients with MDD and high levels measured by the DSST18
of anxiety.25
2.0
Vortioxetine (n=175)
number of correct symbols at week 8

for the treatment of major depressive episodes in * Duloxetine (n=178)

Difference from placebo in DSST –

1.8 1.75
adults.15 It has been proven to be effective where several Figure 2. Vortioxetine improved the MADRS score in
randomized, double-blind, placebo-controlled, active- patients with severe depression16 1.6
referenced, short-term clinical studies found that it 1.4
1.21
Mean change from baseline in MADRS total score
improved the symptoms of depression in adult patients Adults with MADRS ≥30 at baseline (mean baseline MADRS total score 34.0) 1.2
with MDD, as assessed by improvement in MADRS score 1.0
(Figure 2).16–18 Vortioxetine was also shown to significantly
reduce the chances of relapse over 24 weeks by 50% 0
Placebo (n=105) Vortioxetine 5 mg (n=108) 0.8
compared with placebo.19 Venlafaxine XR 225 mg (n=112) Vortioxetine 10 mg (n=100)
0.6
Mean change from baseline

-5
0.4
(MADRS total score)

Its efficacy for the short-term treatment of MDD was -10 0.2
further confirmed in a recent meta-analysis, in which 5, 10
and 20 mg vortioxetine showed significantly greater dose- -15
*
*
0
Change from baseline vs placebo
response improvement from baseline in MADRS score ***
at week 6/8 compared with placebo. 20 The short-term -20 ***
*** ** *p<0.05 vs placebo for change (only for vortioxetine)
***
efficacy of vortioxetine (2.5 to 10 mg/day) on MADRS total -25
***
*** ***
*** ***
***
***
score was sustained throughout a 52-week open-label *** ***
***
extension phase. 21 -30
0 2 4 6 End point
LOCF
Safety and tolerability of vortioxetine in MDD
Vortioxetine in special populations
Treatment week
Vortioxetine is generally well tolerated by patients,
● Patients who responded inadequately to SSRI or with a low rate of discontinuation due to side effects. 27
*p<0.05, **p<0.01, ***p<0.001 vs placebo
SNRI treatment A randomized, double-blind, placebo-controlled, 6-week study; venlafaxine was included The most commonly reported adverse event was mild-
After 8 and 12 weeks of treatment, vortioxetine 10 to
as active reference for study validation, not for comparison of effect sizes to-moderate nausea, which is dose-dependent, but
20 mg/day was found to be significantly superior to
MADRS, Montgomery-Åsberg Depression Rating Scale; XR, extended release;
LOCF, last observation carried forward usually easily manageable. 28,29 Vortioxetine is also
agomelatine in reducing the MADRS total score in weight neutral16,17,24 – it did not cause clinically relevant
patients with MDD who responded suboptimally to one weight changes in adults and the elderly with MDD
course of SSRI or SNRI treatment. The remission rates Vortioxetine improves cognitive function compared with placebo.16,17,24 Moreover, vortioxetine did
achieved with vortioxetine at week 8 and week 12 were In the randomized, double-blind, placebo-controlled not increase the incidence of insomnia or somnolence
40.5% and 55.2%, respectively, in contrast to 29.5% and FOCUS study, vortioxetine 10 and 20 mg/day were relative to placebo. 28
Sexual dysfunction incidence with vortioxetine is also
comparable with placebo. The incidence of TESD
and ASEX total score showed no clinically relevant
difference in symptoms of sexual dysfunction at 5 to
15 mg/day doses of vortioxetine compared with placebo.28
In addition, vortioxetine was superior to escitalopram
in improving SSRI-induced TESD in patients who were
in remission. 30
Key messages
● Vortioxetine is an antidepressant that has been shown
to improve not only mood symptoms, but also cognitive
symptoms of depression.
● Vortioxetine is an effective antidepressant for:
▪ Patients with severe depression;
▪ Depressed patients with high levels of anxiety;
▪ Elderly patients with depression; and
▪ Patients with suboptimal response to SSRI or SNRI
treatment.
● Vortioxetine is weight neutral16,17,24 and generally well-
tolerated by patients, with mild-to-moderate nausea
being reported as the most common adverse effect.
Sexual dysfunction incidence with doses of 5 to 15 mg is
comparable with placebo.

ReCognizing the Vortioxetine Experience

Case study 1: Case study 2: Case study 3:
When the doctor fell ill Confidence no more My brilliant experience

Dr Marvin Chong Swee Woon

Dr Ang Jin Kiat Dr Hazli Zakaria
Consultant Psychiatrist
Senior Lecturer in Psychiatry Psychiatrist and Senior Lecturer
Hospital Fatimah
Universiti Putra Malaysia Universiti Kebangsaan Malaysia
Ipoh

Background Background Background

Dr X is a 26-year-old medical officer with a previous history of
depression during his undergraduate years. He was apparently
well until 4 months before when he decided to stop his medications
due to lethargy and loss of libido. He felt well and managed to
regain his sex drive; however, his depressive symptoms recurred
after 2 months, with poor concentration, forgetfulness and the
inability to multitask affecting his performance at work. He also
began to isolate himself. He lost weight and appetite, and felt
more lethargic and hopeless, but had no suicidal ideation. He saw
a private psychiatrist and was restarted on escitalopram 10 mg
and risperidone 2 mg.
History of current illness
During his first consultation with Dr Ang, the same medications
were continued. After 1 week, he did not show much improvement
and the dose of escitalopram was increased to 15 mg, and then
to 20 mg. His mood and other symptoms improved, as well as his
motivation to work, but his sexual and cognitive issues persisted
and he was still feeling tired.
Experience on vortioxetine
Dr Ang decided to start him on vortioxetine 10 mg daily, which
eventually improved his energy level and cognitive functions, such
as being able to focus better at work, recall better his tasks and
perform the tasks more efficiently. His sex drive and performance
were restored to premorbid state.
Miss T is a 24-year-old, fourth year medical student with a family
history of depression. Her symptoms of depression began after Madam T, who works as an area manager, is
she failed her examinations, which required her to retake the a 35-year-old mother of one boy. She has
course and delay her study by 1 year. She experienced loss been depressed since November 2014, but
of confidence and isolated herself. She also experienced low only sought medical advice in May 2016.
mood on most days and had poor concentration. She had no
suicidal thoughts or psychotic symptoms. She was diagnosed
with moderate MDD. History of current illness
Madam T complained of feeling irritable,
As she preferred non-pharmacological treatment as the first-line emotional, disinterested, worried, fearful,
intervention, she was initially referred for cognitive behavioural indecisive and a lack of confidence. She had
therapy, which improved her mood, sleep and appetite, but not poor concentration and experienced reduced
her self-confidence, concentration and anxiety symptoms. She performance at work. Furthermore, she had
was eventually convinced to receive medications. poor sleep and felt tired easily. She was
diagnosed with MDD.
Experience on vortioxetine
She was started on vortioxetine treatment. She tolerated the Experience on vortioxetine
medication well and her low mood started to improve after 1
week of treatment. Although she was still having persistent After advising her on the possible side effects,
she was prescribed vortioxetine 10 mg once
worries and experiencing some episodes of low mood and
intermittent irritability during the first 3 weeks of treatment, daily. Her overall mood and ability to focus
these symptoms improved as she continued her treatment. improved 2 weeks after treatment, and
Her appetite improved greatly and energy level was regained. the symptoms continued to become better
Currently, her mood is stable and she is being monitored for her throughout her course of treatment. She also
weight as her appetite has improved. She is happy and feels regained her productivity at work and was able
positive about her progress. She has started to reconnect with to make decisions faster. The only side effect
her friends and is confident of completing her study. she experienced was mild nausea.

Abbreviations: ASEX: Arizona Sexual Experience Scale; DSM-5: Diagnostic and Statistical Manual of Mental Disorders Fifth Edition; DSST: Digit Symbol Substitution Test; HAM-A: Hamilton Anxiety Rating Scale; HAM-D24: 24-item Hamilton
Depression Scale; ICD: International Classification of Diseases and Related Health Problems; MADRS: Montgomery-Åsberg Depression Rating Scale; RAVLT: Rey Auditory Verbal Learning Test; RAVLTacq: RAVLT Acquisition; RAVLTdelay:
RAVLT Delayed Recall; UPSA: University of San Diego Performance-based Skills Assessment; SNRI: Serotonin Norepinephrine Reuptake Inhibitor; SSRI: Selective Serotonin Reuptake Inhibitor; TESD: Treatment-emergent Sexual Dysfunction

References: 1. Institute for Public Health (IPH). National Health and Morbidity Survey 2011 (NHMS 2011). Vol. II: Non-Communicable Diseases; 2011. 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders
Fifth Edition (DSM-5®); 2013. 3. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines; 1992. 4. Malhi GS, et al. Aust N Z J Psychiatry 2015;49:1087–1206.
5. Conradi HJ, et al. Psychol Med 2011;41:1165–1174. 6. Iverson GL, Lam RW. Ann Clin Psychiatry 2013;25:135–140. 7. Lam RW, et al. Depress Res Treat 2012;2012:630206. 8. Florida Medicaid Drug Therapy Management Program. Florida
Best Practice Psychotherapeutic Medication Guidelines for Adults; 2015. 9. Lam RW. Can J Psychiatry 2016;61:510–523. 10. McClintock SM, et al. J Clin Psychopharmacol 2011;31:180–186. 11. Sibitz I, et al. J Affect Disord 2010;126(1–
2):245–251. 12. Fried EI, Nesse RM. J Affect Disord 2015;172:96–102. 13. Trivedi MH, et al. Am J Psychiatry 2006;163:28–40. 14. Demyttenaere K, et al. J Affect Disord 2015;174:390–396. 15. MIMS.com. Brintellix. Available at: http://www.
mims.com/malaysia/drug/info/brintellix/. Accessed 29 November 2016. 16. Alvarez E, et al. Int J Neuropsychopharmacol 2012;15:589–600. 17. Boulenger JP, et al. Int Clin Psychopharmacol 2014;29:138–149. 18. Mahableshwarker AR, et al.
Neuropsychopharmacology 2015;40:2025–2037. 19. Boulenger JP, et al. J Psychopharmacol 2012;26:1408–1416. 20. Thase ME, et al. Eur Neuropsychopharmacol 2016;26:979–993. 21. Baldwin DS, et al. Curr Med Res Opin 2012;28:1717–
1724. 22. Montgomery SA, et al. Hum Psychopharmacol Clin Exp 2014;29:470–482. 23. Rush AJ, et al. Am J Psychiatry 2006;163:1905–1917. 24. Katona C, et al. Int Clin Psychopharmacol 2012;27:215–223. 25. Baldwin DS, et al. J Affect
Disord 2016;206:140–150. 26. McIntyre RS, et al. Int J Neuropsychopharmacol 2014;17:1557–1567. 27. Baldwin DS, Hanumanthaiah VB. Future Neurol 2015;10:79–89. 28. Brintellix® summary of product characteristics; 2015. 29. Baldwin
DS, et al. J Psychopharmacol 2016;30:242–252. 30. Jacobsen PL, et al. J Sex Med 2015;12:2036–2048.

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MY-LUN-059

Physically demanding, night shift
work may reduce women’s fertility
RACHEL SOON
J obs which involve shifts outside typical
working hours or heavy physical labour
may negatively impact women’s ability to con-
ceive, according to researchers from Harvard
University’s T.H. Chan School of Public Health.
In an observational study of 473 American
women between 18 to 45 years of age, who
were undergoing fertility treatment in Boston’s
Massachusetts General Hospital between 2004
to 2015, it was found that women who worked
evening, night or rotating shifts produced 2.3
fewer mature oocytes on average compared to
women who worked day-only shifts (p<0.001),
while women who reported lifting or moving
heavy objects at work produced 1.4 fewer than
those who reported never doing so (p<0.007).
[Occup Environ Med 2017; doi: 10.1136/
oemed-2016-103953]
Researchers examined indicators of ovarian
reserve in the patients studied, which included
antral follicle counts and follicle stimulating
hormone (FSH) levels, with higher levels of
the latter indicating dwindling fertility. Ovarian
response, i.e. the number of mature eggs ca-
pable of developing into a healthy embryo, was
also evaluated in 313 of the women who had
completed at least one cycle of In Vitro Fertil-
ization (IVF) by December 2015.
“Our study suggests that women who are
planning pregnancy should be cognizant of the
1-15 APRIL 2017 • I N T E R N AT I O N A L • 39
potential negative impacts that non-day shift
and heavy lifting could have on their reproduc-
tive health,” said Dr. Lidia Mínguez-Alarcón, re-
search fellow in the Department of Environmen-
tal Health and lead author of the study.
Women enrolled in the study were 35 years
old on average, with an average BMI of 23; all
participants were also enrolled in the larger
ongoing EARTH* study, an ongoing prospec-
tive cohort evaluating environmental and di-
etary determinants of fertility. Ovarian reserve
in each participant was evaluated via trans-
vaginal ultrasonography on the third day of an
unstimulated menstrual cycle or progesterone
withdrawal bleed in the year prior to their IVF
cycle. Ovarian response was evaluated by egg
retrieval 35–36 hours after induction of oocyte
maturity, using human chorionic gonadotropin
(hCG).
Using questionnaires, participants reported
how often they lifted or moved heavy objects
in their current job with response options of
‘never’, ‘sometimes’ or ‘often’. Levels of physi-

cal exertion in were categorized as: light (eg,
most time spent sitting, office work), moderate
(eg, lifting/pushing light loads, long periods of
walking) and heavy (eg, lifting, pushing heavy
loads, heavy manual labour). Work shifts were
categorized by day, evening, night or rotating.
With the cohort, four out of 10 women re-
ported that their jobs required them to regu-
larly move/lift heavy objects, and 22% said that
their jobs were moderately to very physically
demanding. Ninety-one percent worked during
normal office hours.
While those with physically demanding jobs
generally had a lower ovarian reserve, it was
also noted that the type of workload did not
seem to impact the participants’ FSH levels.
“These findings have clinical implications, as
Monoclonal antibody linked to
reduced recurrent wheeze in
preterm infants
RACHEL SOON
U sage of monoclonal antibody palivizum-
ab to prevent respiratory syncytial virus
(RSV) infection may also reduce development
of recurrent wheeze in preterm babies over the
long term.
In a 6-year follow-up study examining the
effectiveness of palivizumab in prevention of
1-15 APRIL 2017 • I N T E R N AT I O N A L • 40
women with fewer mature oocytes would have
fewer eggs which are capable of developing
into healthy embryos,” said the researchers.
“Occupational factors may be more specifically
affecting oocyte production and quality, rather
than accelerating ovarian ageing.”
The researchers cautioned that the findings
were based on couples attempting to conceive
with medical assistance, and might not reflect a
broader demographic. In addition, they noted
that they were unable to assess the impact of
other potentially influential factors such as long
working hours or alternating between day and
night shifts.
*EARTH: Environment and Reproductive
Health study
atopic asthma in 444 Japanese infants born at
33 to 35 weeks’ of gestation, researchers re-
ported that while the drug did not prevent on-
set of atopic asthma, it did appear to reduce—
though not eliminate—physician-diagnosed
recurrent wheezing up to 6 years of age. [Am
J Respir Crit Care Med 2017;doi: 10.1164/
rccm.201609-1812OC]
“These results suggest that atopic asthma in

children up to age 6 is probably not due to RSV,
but a significant proportion of recurrent wheeze
is,” said lead study author Professor Hiroyuki
Mochizuki, chairman of paediatrics at Tokai
University, Japan. “Our findings suggest two in-
dependent phenotypes of recurrent wheezing
in young children: one that is dependent and
one that is independent of RSV lower respira-
tory tract infection.”
Of the 444 infants enrolled in the multicentre
case-control study, 349 received palivizumab
within the first year of life during the 2007–2008
RSV season. Recurrent wheezing was defined
as the occurrence of three or more episodes of
expiratory wheezing diagnosed by a physician
in a 12-month period; expiratory wheezing, in
turn, was defined as a bronchial obstruction
lasting for at least 24 hours preceded by at
least a 1 week of non-wheezing healthy period.
Infants who received at least three doses
of palivizumab had about half the incidence of
physician-diagnosed wheeze by age 6, com-
pared to those who did not receive the drug
(15.3% versus 31.6%, p=0.003). On the other
hand, prevalence of atopic asthma—the study’s
primary endpoint—was found to be not signifi-
cantly different. (15.3% versus 18.2%; p=0.57)
According to the researchers, the strength of
the study was that it was long-term prospective
study in 52 centres with a high follow-up rate
(75% of children completed the 6 year follow-
up). Parents reported their physician’s assess-
ments of recurrent wheezing in their children
1-15 APRIL 2017 • I N T E R N AT I O N A L • 41
via a report card and a mobile phone-based
internet reporting system.
Study limitations noted by the researchers
include potential bias due to lack of randomiza-
tion; there was minimal difference in family his-
tories of asthma, birth weight and gestational
age among infants who received palivizumab
treatment and those who did not. It was also
observed that children in the untreated group
were more likely to live in a home with a smoker
and have a family member with a history of al-
lergies.
“Long-term observation of these subjects is
planned to consider the impact of RSV infection
on lung function in later life,” said Mochizuki.
The US Centers for Disease Control and
Prevention (CDC) notes that RSV is the most
common cause of lower respiratory tract infec-
tions among young children worldwide. Infec-
tion rates tend to peak during the annual rainy
season in tropical countries, with outbreaks
lasting up to five months. [Rev Med Virol
2014;24(1):15–34]

Predictor of cardiac function
linked to low-grade exercise
tolerance in COPD
DR. ANGELA V. IGNACIO
A n association exists between decreased
left ventricular stroke volume (LVSV) and
tolerance for low-grade exercise among indi-
viduals who have stable chronic obstructive
pulmonary disease (COPD), suggests a Japa-
nese study.
The single-centre study included 57 male
(n=54) and female (n=3) patients with stable
COPD without any reported exacerbations in
the past 3 months. Participants did not have
heart failure or orthopaedic disease that may
affect their ability to perform the 6-minute walk
test (6MWT).
The 6MWT is a simple and practical test
used to assess exercise tolerance in patients
with COPD, with guidelines set by the Ameri-
can Thoracic Society. It has been used for
measuring treatment response in patients with
moderate to severe heart or lung disease, as
well as predicting morbidity and mortality. [Am
J Respir Crit Care Med 2002;166:111–ß7]
In this study, researchers measured the dis-
tance each participant could quickly walk on
a flat, hard-surfaced corridor within a 6-minute
period; participants were allowed to rest if they
experienced fatigue or dyspnoea, then advised
to resume walking once symptoms improved.
The cutoff value for low-grade exercise toler-
1-15 APRIL 2017 • I N T E R N AT I O N A L • 42
COPD exacerbations accelerate lung function decline,
especially for mild COPD.
ance was a 6MWT distance of <350 meters.
Cardiac function was assessed using echo-
cardiography and 64-slice multidetector com-
puted tomography (MDCT). Respiratory func-
tion was also evaluated.
Researchers found that among the cardiac
MDCT and pulmonary function parameters, the
forced expiratory volume in 1 second (FEV1),
percent predicted FEV, left ventricular end
diastolic volume and left ventricular cardiac
output had a significantly positive correlation
with 6MWT distance. [BMJ Open Respir Res
2017;4:e000158]
Moreover, both univariate and multivariate
analyses demonstrated that a decreased LVSV
was most closely associated with a decreased
walked distance in the 6MWT.
Based on study findings, researchers pos-
ited that LVSV is a significant predictive factor

for low-grade exercise tolerance in patients
with COPD.
In addition, researchers suggested that car-
diac CT scanning would offer some benefits in
evaluating cardiac function and coronary ath-
erosclerosis in this population, as COPD and
coronary artery disease appear to coexist fre-
quently. Apart from having cigarette smoking
as a common risk factor, various studies have
1-15 APRIL 2017 • I N T E R N AT I O N A L • 43
shown that COPD is characterized by systemic
inflammation, which is also associated with in-
creased cardiovascular risk, progression of ath-
erosclerosis and other cardiovascular-related
adverse events. This, in turn, contributes to in-
creased mortality risk, which is why early diag-
nosis and intervention for cardiac comorbidities
is important. [Proc Am Thorac Soc 2008;5:543–
548; Eur J Heart Fail 2009;11:130–139]
Hong Kong Institute of Musculoskeletal Medicine

AN UPDATE ON
2– 0 17
MUSCULOSKELETAL 7 9 JULY

MEDICINE SKILLS HONG

KONG
1: 4 Faculty to Attendees Ratio

FACULTY MEMBERS
Keith Chan, Hong Kong Stanley Lam, Hong Kong Regina Sit, Hong Kong
Kevin Chang, Taiwan Paco Lee, Hong Kong Daniel Wang, Taiwan
Pon-an Chen, Taiwan Carina Li, Hong Kong Ricky Wu, Hong Kong
Antonio Gregory, Hong Kong Frederick Lin, Taiwan Chi-hung Yen, Hong Kong
Andrew Ip, Hong Kong Allen Ngai, Hong Kong Chi-kai You, Taiwan
Mark Lai, Hong Kong

WHO SHOULD ATTEND? VENUE

• Family Physicians
• Musculoskeletal Physicians
• Rehabilitation and Pain Physicians
• Sports Physicians
REGISTRATION
The registration fee is HK$20,000 / US$2,560.
It includes two days ultrasound guided cadaver
injection workshop.
Please register at www.hkimm.hk.
ACADEMIC ACCREDITATIONS
CME and CPD points will be applied from
relevant colleges and associations in Hong Kong.
Day 1:
Ballroom, 2/F., Courtyard by Marriott
1 On Ping Street, Shatin, Hong Kong
Day 2&3:
Room 306, 3/F., Choh-ming Li Basic Medical
Sciences Building
The Chinese University of Hong Kong,
Shatin, Hong Kong
FURTHER INFORMATION
Please visit www.hkimm.hk or
contact the meeting secretariat at
(852) 2155 8557 or 3153 4374 or send
e-mail to meeting.hk@mims.com
Grow with

Connecting over
2 million healthcare
professional across Asia

MIMS Career is for both employers and jobseekers

For more information, visit: doctor-job.mims.com
nurse-job.mims.com
healthcare-job.mims.com

Cervicovaginal microbiome
composition affects HIV risk
AUDREY ABELLA
W omen with cervicovaginal bacterial com-
munities that are high in diversity but low
in Lactobacillus abundance may be at increased
risk of acquiring HIV, shows the FRESH* study.
This prospective cohort study that monitored
236 healthy South African women 18–23 years
of age identified four distinct types of bacterial
communities referred to as ‘cervicotypes’ (CTs)
ie, Lactobacillus crispatus (CT1), Lactobacillus
iners (CT2), Gardnerella vaginalis (CT3), and
another bacterial genus other than Gardnerella
or Lactobacillus as the dominant taxon (CT4).
[Immunity 2017;46:29–37]
“None of the women who acquired HIV had
[a Lactobacillus] crispatus-dominant commu-
nity. Women with CT2 communities were also
underrepresented among participants who
subsequently acquired HIV relative to the un-
infected group, while those with CT3 and CT4
communities were more prevalent among
women who went on to become infected,” said
the researchers.
There was a fourfold increased risk of HIV
acquisition in participants with a highly di-
verse, Lactobacillus-deficient cervicovaginal
bacterial community (58%) dominated by ei-
ther CT3 (n=68, hazard ratio [HR], 4.22, 95%
confidence interval [CI], 1.06–16.88; p=0.042)
or CT4 (n=70, HR, 4.03, 95% CI, 1.14–14.27;
p=0.031).
1-15 APRIL 2017 • I N T E R N AT I O N A L • 46
Certain species of vaginal bacteria can increase a wom-
an's susceptibility to HIV.
After adjusting for Chlamydia infection, the
risk remained significantly increased in women
with CT4 communities (HR, 4.41, 95% CI, 1.17–
16.61; p=0.028)
CT1 was dominant in the low-diversity com-
munities identified in 10% (n=23) of the partici-
pants, while CT2 was found in 32% (n=74).
Of note was the lack of distinct viral commu-
nities, which the researchers suggested high-
lighted the role of bacteria in modifying the risk
of HIV acquisition.
“The increased rate of HIV acquisition in
women with high-diversity, low Lactobacillus
abundance bacterial communities observed in
our study could be explained by the sensing
of specific bacterial antigens or components
such as lipopolysaccharide … [which] likely re-
sults in activation and recruitment of HIV target
cells to the female genital mucosa,” said the
researchers.

Given the high prevalence of HIV in young
African women, a comprehensive understand-
ing of factors that affect HIV acquisition and
identifying advanced regimens that could po-
tentially reduce the risk are essential, noted the
researchers.
“Our results advance our understanding of
the cervicovaginal microbiome as an HIV risk
1-15 APRIL 2017 • I N T E R N AT I O N A L • 47
factor and demonstrate the importance of con-
sidering the microbiome in the development of
new treatments and preventive strategies to re-
duce HIV acquisition in young women living in
sub-Saharan Africa,” they said.
*FRESH: Females Rising through Education,
Support and Health study
1-15 APRIL 2017 • H U MO U R • 48
1-15 APRIL 2017 • F O R SA L E • 49
 1-15 APRIL 2017 • F O R SA L E • 50

CLINIC FOR SALE

--------------------------------------------------------------------------
Klinik Skudai, Taman Nesa,
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Tel : (016)7459901
Email : urban26@hotmail.com

A short list of equipment:

Ultrasound m/c, ECG, x-ray viewer, oxygen cylinder,
other general necessary equipment and complete
security system.

CLINIC FOR SALE/PARTNERSHIP

--------------------------------------------------------------------------
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Contact: Dr. Lee 03-6120 3718 / Mrs. Lee 012-697 9323
 1-15 APRIL 2017 • F O R SA L E • 51

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 1-15 APRIL 2017 • C A L E N DA R • 52

ANNOUNCEMENT

Inaugural World Congress in Anti-Aging, Aesthetic, Regenerative,

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Go
Beyond
the
Clinic
Dear Doctors,
What do you do when you leave the clinic? Is there life beyond the clinic? Is
there a passion that keeps you sane throughout the day, and leaves you
raring to go the moment you complete your shift and step out of that door?

would like to invite you to share your passion

and obsession with the rest of the medical fraternity.

Do submit your stories and pictures to enquiry.my@mims.com.

Share your PASSION. –Ed.

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