october 2014

Novel agent outperforms

ACE inhibitor in large
HF trial

FORUM
PARADIGM-HF:
Heralding a new
approach in HF
treatment

drug
profile
Novel therapy for
HER2-positive
metastatic breast
cancer

news
Novel dengue
vaccine coming up

RESEARCH
REVIEWs
Korean red
ginseng beneficial
for women with
premenstrual
syndrome

O c to b e r 2 01 4

Novel agent outperforms ACE

inhibitor in large HF trial
Christina Lau

he investigational agent LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI),

has demonstrated superior efficacy to a widely

used ACE inhibitor (ACEi) in the treatment of
patients with chronic heart failure, according
to a study presented at the recent European
Society of Cardiology (ESC) Congress in Barcelona, Spain.
In the PARADIGM-HF* trial, LCZ696, a combination of the ARB valsartan and neprilysin
inhibitor sacubitril, showed a significant 20

The PARADIGM-HF study, involving 8,399 patients with

HF, saw novel ARNI agent LCZ696 outdo enalapril in
major primary CV outcomes.

percent greater effect over enalapril 20 mg/day

in reducing cardiovascular death or hospital-

The ARNI also reduced all-cause mortality,

ization for heart failure (21.8 vs 26.5 percent;

a secondary endpoint of the trial, by an incre-

p=0.0000002). [N Engl J Med 2014, e-pub 30

mental 16 percent compared with enalapril (17

Aug, DOI: 10.1056/NEJMoa1409077]

vs 19.8 percent; p<0.0001).

When components of the composite prima-

Symptoms and physical limitations of heart

ry endpoint were analyzed separately, LCZ696

failure, measured on the Kansas City Cardio-

demonstrated a 20 percent greater reduction

myopathy Questionnaire (KCCQ) at 8 months,

in cardiovascular death (13.3 vs 16.5 percent;

significantly improved in patients receiving

p=0.00004) and a 21 percent greater reduction

LCZ696 vs enalapril (KCCQ score, -2.99 vs

in hospitalization for heart failure (12.8 vs 15.6

-4.63; p=0.001).

percent; p=0.0004) compared with enalapril.

Enalapril 20 mg/day is the current gold-

The trial was stopped early in April, after

standard therapy in [chronic heart failure,

a median follow-up of 27 months, for an over-

CHF]. Results of the PARADIGM-HF trial pro-

whelming benefit of LCZ696 on cardiovascular

vide compelling evidence that LCZ696 should

mortality, said co-principal investigator Dr. Mil-

replace current use of ACEIs and ARBs in the

ton Packer of the Southwestern Medical Center

management of patients with mild to moder-

in Dallas, Texas, US.

ately severe CHF, said Packer.

O c to b e r 2 01 4

The major benefit of LCZ696 is that it chang-

Although more symptomatic hypotension

es the natural course of CHF, he pointed out.

was reported with LCZ696, this rarely required

It doubles the benefit of current cornerstone

treatment discontinuation, he continued. Im-

treatment with ACEIs, which reduce cardiovas-

portantly, LCZ696 was not associated with an

cular death by 18 percent vs placebo.

increased risk of serious angioedema, which

The PARADIGM-HF trial included 8,399 pa-

was the main safety concern observed with a

tients with class II to IV heart failure and an

related medication known as omapatrilat in an-

ejection fraction of 40 percent or below. The

other trial.

patients were randomized to receive LCZ696

The survival advantage demonstrated in the

200 mg twice daily (n=4,187) or enalapril 10

trial has prompted the US FDA to grant Fast

mg twice daily (n=4,212), in addition to recom-

Track status to LCZ696. Its developer Novartis

mended therapy.

expects the FDA review to be completed by the

LCZ696 was better tolerated than enala-

end of 2014.

pril, reported Packer. It was less likely than

enalapril to cause cough, hyperkalemia or re-

*PARADIGM-HF: Prospective Comparison of ARNI with

nal impairment, and less likely to be discontin-

ACEI to Determine Impact on Global Mortality and Mor-

ued due to an adverse event.

bidity in Heart Failure.

O c to b e r 2 01 4

Different, co-occurring respiratory

illnesses increase lung cancer risk
Chuah Su Ping

to lung cancer, but

not longer (OR=3.31;

ndividual respiratory diseases are differen-

2.33-4.70

tially associated with lung cancer after ac-

Asthma had an inverse

counting for co-occurring previous respira-

association with lung

tory disease (PRD), concluded a large pooled

cancer, and no asso-

analysis of seven studies involving more than

ciation was observed

25,000 individuals. [Am J Crit Care Med 2014

between tuberculosis

Jul 23. Epub ahead of print. PMID:25054566]

and lung cancer after

Associations between various respiratory

diseases and lung cancer have been shown
in earlier studies, but few of these studies con-

for

men).

accounting for confounding factors.

In

particular,

the

sidered multiple respiratory diseases simulta-

investigators

neously, said researcher Dr. Ann Olsson, of

that patients with co-

the International Agency for Research in Lyon,

occurring chronic bronchitis, emphysema and

France. In our pooled analysis of seven case-

pneumonia had a higher risk of lung cancer

controlled studies involving more than 12,500

than those with chronic bronchitis only. There

cases and 14,900 controls, we found associa-

was no association between chronic bronchitis

tions between lung cancer and chronic bron-

and lung cancer among patients with co-occur-

chitis, emphysema, and pneumonia, with a

ring asthma or tuberculosis.

greater increased lung cancer risk among subjects with all three of these conditions.

noted

A large pooled analysis

has examined links
between respiratory
diseases and lung cancer
risk.

The variations in the associations between

lung cancer and different patterns of previous

Olsson and colleagues reported that chronic

respiratory diseases that we observed in our

bronchitis and emphysema were positively asso-

study may indicate differences in the under-

ciated with lung cancer, after accounting for oth-

lying etiological mechanisms, said Olsson.

er respiratory diseases and smoking (OR=1.33;

Better understanding of these associations

95% CI 1.20-1.48 for men). A positive relationship

may help guide the type and frequency of clini-

was also observed between lung cancer and

cal surveillance needed for patients with each

pneumonia diagnosed two or fewer years prior

of these diseases.

O c to b e r 2 01 4

FORUM

PARADIGM-HF: Heralding a new

approach in HF treatment
Chuah Su Ping

the management of HF in Malaysia recommends

the use of ACEIs as first-line treatment for HF and

he results of the PARADIGM-HF* study were

in all patients in whom there is evidence of left

received with enthusiasm by the medical

ventricular (LV) systolic dysfunction as reflected

community worldwide, with many believing that

by an LV ejection fraction of <40 percent. [2007

it may influence and potentially change current

Clinical Practice Guidelines: Management of

clinical practice for heart failure (HF).

heart failure. Ministry of Health Malaysia. Avail-

Given the survival advantage of LCZ696

over currently available drugs, once this drug

able at www.moh.gov.my/attachments/3894.pdf.
Accessed on 22 September 2014]

becomes available, it would be difficult to un-

I certainly believe the results of the PARA-

derstand why physicians would continue to use

DIGM-HF trial will affect current treatment prac-

traditional angiotensin converting-enzyme inhib-

tice in Malaysia. We are currently still in discus-

itors (ACEIs) or angiotensin receptor blockers

sion as to how we would update the current

(ARBs) for the treatment of heart failure, said

CPG based on these new and compelling data,

co-primary author of the study Dr. Milton Packer

said Zambahari, who sits on the CPGs expert

from the University of Texas Southwestern Medi-

panel. We also hope that based on the results,

cal Center in Dallas, Texas, US.

the relevant bodies will be able to fast-track the

availability and possible reimbursement of the

Regional experts weigh in

Heart failure is a growing problem in Ma-

drug, so that the benefits of this drug can reach

the patients in need.

laysia, especially among women. It is an im-

Zambahari noted that in PARADIGM-HF, the

portant cause of hospitalization accounting for

significant benefits of LCZ696, an angiotensin

about 10 percent of all medical admissions in

receptor-neprilysin inhibitor (ARNI), were ob-

Malaysia, and about 45 percent of patients with

served in a specific group of patients, namely

heart failure are readmitted at least once within

patients with New York Heart Association (NYHA)

12 months for acute decompensation, said

class II to IV HF and an ejection fraction of 40

Professor Robaayah Zambahari, senior con-

percent or less. We do not know yet how well

sultant cardiologist and chief executive director

LCZ696 may benefit all heart failure patients.

of the National Heart Institute in Kuala Lumpur,

For now, we are still awaiting the results of the

Malaysia.

PARAGON-HF** trial which will assess the effect

Current clinical practice guidelines (CPG) for

of LCZ696 on cardiovascular death and total HF

hospitalizations in HF patients with preserved

ejection fraction [HF-pEF], a group of patients
for whom good therapy is still lacking.

O c to b e r 2 01 4

FORUM

of the drug in Singapore.

However, Lam does believe that the broad
media coverage, which accompanied the announcement of the PARADIGM-HF results, was

Key study findings

a bit sensationalized. This can be dangerous,

The very powerful message we got from this

she said. We need to remember that at the end

study is that LCZ696 not only reduces readmis-

of the day, the ARNI is still an ARB, so it can still

sion, it also reduces morbidity and CV mortal-

carry a risk of hyperkalemia. There are certainly

ity, said Dr. David Sim, a consultant at the De-

HF patients for whom this drug would not be

partment of Cardiology and director of the Heart

suitable.

Failure Programme at the National Heart Cen-

With regards to patient selection, we know

tre, Singapore. The study challenges the use

based on the patient criteria that LCZ696

of ACEIs, with the aim of replacing it and not

showed a benefit in a specific group of NYHA

for use as an add-on therapy. This study tells

class II to IV heart failure patients, said Lam.

us that by switching from an ACEI or an ARB to

For NYHA class IV patients, it is important to

an ARNI, we may be able to significantly reduce

assess each patient individually to determine if

mortality and morbidity in heart failure patients.

they could potentially benefit from the drug.

Sim is also looking forward to the results of

She noted that while Asians were well-rep-

the PARAGON-HF trial, which is currently un-

resented in the study 18 percent of the study

derway. However, based on the strength of the

population she would look forward to seeing a

PARADIGM-HF study results, I would personally

regional sub-study carried out on a purely Asian

favor recommending this drug to HF patients

population. But for now, these results simply

who could potentially benefit from it.

cannot be ignored, and there is no doubt that

this will result in a literal paradigm shift in clinical

Caution still needed when prescribing

practice.

The evidence from PARADIGM-HF is certainly irrefutable, said Associate Professor

*PARADIGM-HF: Prospective Comparison of ARNI (Angio-

Carolyn Lam of the Cardiac Department at the

tensin Receptor-Neprilysin Inhibitor) with ACEI (Angioten-

National University Heart Centre, Singapore.

sin-Converting Enzyme Inhibitor) to Determine Impact on

This is a drug which has beaten the gold stan-

Global Mortality and Morbidity in Heart Failure

dard of heart failure treatment by a significant

** PARAGON-HF: Prospective comparison of ARNI with

margin. She said that based on these results,

ARB Global Outcomes in Heart Failure with Preserved

she would certainly support the reimbursement

Ejection Fraction

O c to b e r 2 01 4

N E WS

Novel dengue vaccine coming up

Dr. Joslyn Ngu

phase III clinical study is currently underway to test the efficacy of a live attenuated

tetravalent vaccine for dengue.

The objective of the study is to assess the
efficacy, safety and immunogenicity of the vaccine in preventing symptomatic virologicallyconfirmed dengue cases, regardless of severity
or serotype, said Dr. Muruga Vadivale, senior director of Dengue Medical Affairs Asia-Pacific at
Sanofi Pasteur, Singapore.
In the study, priority was given to countries
with the most urgent and unmet needs, said

The new dengue vaccine may reduce disease burden

Muruga. This is why one of the earlier phase

globally.

III trials, CYD14, was conducted in the Southeast Asian (SEA) region. A total of 10,275 par-

efficacy, the vaccine also had a good safety pro-

ticipants aged between 2 and 14 years were

file over the entire 25-month follow-up period,

recruited from Thailand, Indonesia, Malaysia,

added Muruga.

Vietnam and the Philippines. All participants

I think today we are at the brink of revers-

were randomized and given the vaccine or sa-

ing the tide against dengue. We have a vaccine

line injections at 0, 6 and 12 months. For each

that may be [introduced] after the next phase

participant given placebo, there were two who

III study in South America and we have future

were given the vaccine.

vaccine candidates from other countries as well.

The results showed that CYD14 achieved its

We might just be able to reverse the tide against

primary endpoint. Based on per protocol (PP)

dengue, said Muruga. The additional data from

analysis, the overall vaccine efficacy was 56.5

the South America study will help researchers

percent, said Muruga. More importantly, for all

better understand the efficacy and safety of the

dengue serotypes, PP analysis showed that

vaccine in different populations.

the vaccine reduced dengue hemorrhagic fever

Muruga said there are currently five other tet-

(DHF) cases by 88.5 percent and intention-to-

ravalent dengue candidates in the pipeline two

treat (ITT) analysis showed a reduction of 67.2

live attenuated vaccines, an inactivated vaccine,

percent for hospitalized dengue cases. Besides

a subunit vaccine and a DNA vaccine. These vac-

O c to b e r 2 01 4

N E WS

cines are in phase I or II of clinical study. [Available

increasing incidence rate and burden caused

at: http://www.who.int/immunization/research/de-

to both the patient and society. Additionally, the

velopment/WHO_dengue_vaccine_QA_July2014.

inadequacy of disease prevention and control,

pdf?ua=1. Accessed on 21 August 2014]

and lack of specific treatment and prophylactic

A dengue vaccine is needed because of the

measures also contribute to the need.

Fenofibrate equally effective for male,

female T2DM patients
Dr. Joslyn Ngu

The FIELD study, on the other hand, recruited a large number of women. Of the total 9,795

ccording to a study, fenofibrate is as effec-

participants with T2DM, 3,657 were women and

tive in women as in men for the treatment of

6,138 men. The study aimed to discover if there

type 2 diabetes mellitus (T2DM) in terms of car-

is any difference in the benefits and side effects

dioprotection and improving dyslipidemia.

between both sexes. The participants were given

The study was conducted by the Fenofibrate

Intervention and Event Lowering in Diabetes

either a daily fenofibrate (200 mg/day) or placebo

tablet for 5 years.

(FIELD) researchers in Australia, New Zealand

The researchers, led by Professor Anthony

and Finland. Earlier in 2005, they published a

Keech, of the clinical trials center, University

report that showed fenofibrate could reduce the

of Sydney, and Associate Professor Michael

rates of diabetic complications. However, recent-

dEmden, of the endocrine research unit, Royal

ly, the ACCORD (Action to Control Cardiovas-

Brisbane Hospital, Australia, found that women

cular Risk in Diabetes) lipid trial in the US found

on fenofibrate had a bigger reduction in terms of

that fenofibrate was not advantageous to some

adverse blood fats, and total low-density-lipopro-

women.

tein (LDL) and non-high-density-lipoprotein (HDL)

Antecedent fenofibrate studies did not show a

cholesterol and apolipoprotein B than men. This

sex difference in outcomes. This could be partly

was regardless of their menopausal status and

due to the fact that majority of the bigger cardio-

statin intake.

vascular intervention studies with fibrate mono-

The results showed a 30 percent decrease

therapy either excluded women or had relatively

in the risk of a cardiovascular outcome in

small amounts of women participants.

women compared to 13 percent in men. As for

O c to b e r 2 01 4

N E WS

patients at high-risk of diabetic complications

T2DM. Both sexes with T2DM should be consid-

due to high triglyceride and low HDL-choles-

ered for fenofibrate therapy for cardioprotection

terol levels, fenofibrate decreased the risk of

... especially those with abnormal blood fats (dys-

cardiovascular outcomes by 24 percent in men

lipidemia), concluded the authors.

and 30 percent in women.

Fenofibrate is a lipid drug used to reduce the

Fenofibrate improved the lipoprotein profile

amount of triglycerides and small dense LDL-

more in women than men. Cardiovascular event

cholesterol, and at the same time, increase the

reductions with fenofibrate were consistently sim-

levels of HDL-cholesterol in the body. It is con-

ilar in women and men, including among those

traindicated in fenofibrate hypersensitivity, he-

with low HDL-cholesterol and high triglyceride

patic or severe renal dysfunction, pre-existing

levels. These data provide reassurance about fe-

gallbladder disease, pregnancy and lactating

nofibrate efficacy in both women and men with

mothers.

O c to b e r 2 01 4

N E WS

10

Large genomic study sheds new light

on schizophrenia
Alexandra Kirsten

these genes are controlling pathways involved

in signaling between brain cells and synaptic

ver 100 locations in the human genome

plasticity, a function essential to learning and

have been linked to a raised risk of develop-

memory, provides biological plausibility for the

ing schizophrenia in the largest study of its kind.

findings.

By studying the genome, we are getting a better

Many of these findings may have the po-

handle on the genetic variations that are making

tential to provide entirely new insights into the

people vulnerable to psychiatric disease, ex-

cause and management of schizophrenia. By

plained Dr. Tom Insel, director of the National In-

discovering an association between the illness

stitute of Mental Health, Bethesda, Maryland, US,

and the region of the genome that holds DRD2

which helped fund the study. Through the won-

the gene that produces the dopamine recep-

ders of genomic technology, we are in a period

tor targeted by all approved medications for

in which, for the first time, we are beginning to

schizophrenia the study suggests that other

understand many of the players at the molecular

uncovered loci may point to additional thera-

and cellular level.

peutic targets.

In the multi-stage schizophrenia genome-

The fact that we were able to detect genetic

wide association study (GWAS) more than

risk factors on this massive scale shows that

80,000 genetic samples from schizophrenic

schizophrenia can be tackled by the same ap-

patients and healthy volunteers were evalu-

proaches that have already transformed our

ated. [Nature 2014; July 22. doi:10.1038/na-

understanding of other diseases, concluded

ture13595]

study author Dr. Michael ODonovan, deputy

The scientists identified 108 specific loca-

director of the MRC Centre for Neuropsychiat-

tions in the human genome associated with a

ric Genetics and Genomics at Cardiff University

risk for schizophrenia. Eighty-three of those loci

School of Medicine, Wales, UK. The wealth of

had not previously been linked to the illness.

new findings have the potential to kick-start the

The associations were enriched among

development of new treatments in schizophre-

genes expressed in the brain, particularly those

nia, a process which has stalled for the last 60

related to neuronal and synaptic function. That

years.

O c to b e r 2 01 4

dr u g p r ofi l e

11

Trastuzumab emtansine: Novel

therapy for HER2-positive metastatic
breast cancer
Trastuzumab emtansine (Kadcyla, Roche Pharmaceuticals) underwent priority review,
and was subsequently approved by the US Food and Drug Administration in 2013 for the
treatment of patients with HER2-positive metastatic breast cancer who have previously
received trastuzumab and a taxane separately, or in combination. This is the first targeted
chemotherapy agent approved for use in this patient population.

Ee Lyn Tan, PhD

Introduction
Breast cancer could be classified based on
pathology and biomarkers. At the time of biopsy, biomarkers including estrogen and progesterone receptor status and human epidermal
growth factor receptor 2 (HER2) are evaluated.
HER2-neu gene amplification, leading to HER2
overexpression, could be found in about 30 percent of breast cancers. [Science 1987;235:177182] Those with HER2-positive breast cancers
tend to have more aggressive disease and poorer outcomes than those who are HER2-negative.
[New Engl J Med 2001;344:783-792]
Trastuzumab is a humanized anti-HER2
monoclonal antibody considered to be the current gold standard treatment for HER2-positive

ing treatment adverse effects. [Future Oncol

breast cancer. While single-agent HER2-target-

2013;9:1-11]

ed therapy is considerably well-tolerated, less

Trastuzumab emtansine (T-DM1) comprises

than one in three patients will have a tumor re-

a monoclonal antibody that targets HER2 re-

sponse. For this reason, concomitant chemo-

ceptors on breast cancer cells and emtansine,

therapy is typically prescribed thereby increas-

a small molecule cytotoxin.

O c to b e r 2 01 4

dr u g p r ofi l e

12

Trastuzumab emtansine

cally achieved by cycle two. All pharmacokinet-

Mode of action

ic parameters are consistent at cycle one and

T-DM1 is a novel antibody-drug conjugate

in later cycles with no significant accumulation

composed of the cytotoxic agent DM1 (a mi-

of T-DM1 following the 3-weekly dosing cycle.

crotubule inhibitor) conjugated to trastuzumab

[KADCYLA Full Prescribing Information]

via a stable thioether linker, thereby primarily

targeting chemotherapy delivery to cells over-

Efficacy

expressing the HER2 receptor. [Future Oncol

The efficacy of T-DM1 has been established

2013;9:1-11] Therefore, it can be said that the

through extensive preclinical work. Several

mechanism of action of T-DM1 is two-fold: it ex-

phase I clinical trials have been conducted

erts a direct antitumor effect with trastuzumab,

to examine its pharmacokinetics, safety and

and at the same time a cytotoxic effect from the

maximum tolerated dose. Based on these pre-

chemotherapy component of the agent.

liminary efficacy results, there have been three

Upon HER2 receptor binding, T-DM1 undergoes internalization and subsequent lysosomal

phase II studies. [Breast Cancer 2014;6:103113]

degradation. This results in intracellular release

In the largest randomized phase II clinical

of DM1-containing cytotoxic catabolites. When

trial, 137 patients with HER2-positive meta-

DM1 binds to tubulin, cell microtubule networks

static or locally advanced breast cancer were

are disrupted resulting in cell cycle arrest, sub-

randomly assigned to receive either trastu-

sequent apoptosis and cell death. T-DM1 also

zumab plus docetaxel (n=70) or T-DM1 (n=67)

inhibits HER2 receptor signaling, facilitates

as first-line treatment until disease progression

antibody-dependant cell-mediated cytotoxicity

or unacceptable toxicity. Results showed me-

and inhibits shedding of the HER2 extracellu-

dian progression free survival (PFS) was 14.2

lar domain in human breast cancer cells that

months in the T-DM1 arm compared with only

overexpress HER2. [KADCYLA Full Prescribing

9.2 months in the trastuzumab plus docetaxel

Information]

arm. Overall response rate (ORR) in the T-DM1

arm was 64 percent versus 58 percent in the

Pharmacokinetics
T-DM1 exhibits nonlinear pharmacokinetics

trastuzumab/docetaxel arm. [J Clin Oncol

2013;31:1157-1163]

at doses less than 2.4 mg/kg, after which linear-

There are numerous phase III studies on

ity is established. Based on population phar-

T-DM1, many of which are still ongoing. EMIL-

macokinetic analysis, the central volume of dis-

IA* is the landmark phase III study for T-DM1.

tribution is 3.13 L. The cytotoxic component of

In this trial, 991 patients with advanced HER2-

T-DM1 is mainly metabolized by CYP3A4, and

positive breast cancer, whose disease had pro-

to a lesser extent CYP3A5. The median half-life

gressed through treatment with trastuzumab

of T-DM1 is 4.5 days, and steady state is typi-

and a taxane, were randomized to T-DM1 alone

O c to b e r 2 01 4

d r u g p r ofi l e

13

or lapatinib plus capecitabine. Median PFS was

one patient on T-DM1 developed Grade 3 left

significantly prolonged with T-DM1 by approxi-

ventricular systolic dysfunction. [New Engl J

mately 3 months (9.6 vs 6.4 months; p<0.001).

Med;367:1783-1791] In the phase II Hurvitz

T-DM1 also significantly improved median over-

study, only one patient in the T-DM1 group de-

all survival (30.9 vs 25.1 months; HR, 0.68, p<

veloped a left ventricular ejection fraction of

0.001). The objective response rate was high-

<40 percent, although no symptoms were re-

er with T-DM1 than lapatinib plus capcitabine

ported. [J Clin Oncol 2013;31:1157-1163]

(43.6 percent, vs 30.8 percent; p<0.001). Estimated 1-year survival rates were 85.2 percent

Dosing

for patients treated with T-DM1 (78.4 percent in

The recommended dose of trastuzumab

the lapatinib plus capecitabine arm). [New Engl

emtansine is 3.6 mg/kg given as an intrave-

J Med 2012;367:1783-1791]

nous infusion every 3 weeks (21 day cycle)

until disease progression or unacceptable tox-

Safety

icity. Doses above 3.6 mg/kg should not be

T-DM1 is generally well tolerated and does

used. Trastuzumab emtansine should not be

not appear to be associated with chemother-

substituted with trastuzumab. [KADCYLA Full

apy-related neuropathy. Nevertheless, T-DM1

Prescribing Information]

has been approved by the US FDA with a

The first infusion should be administered

boxed warning for cardiac, embryo-fetal and

over 90 minutes. During this time, and for at

hepatotoxicity. [KADCYLA Full Prescribing In-

least 90 minutes following this initial dose, pa-

formation]

tients should be observed for fever, chills and

In the EMILIA study, rates of Grade 3 or 4

other infusion-related reactions. If the first infu-

adverse events were higher in the lapatinib/

sion is well tolerated, all subsequent infusions

capecitabine than in the T-DM1 arm (57 per-

can be administered over 30 minutes. Patients

cent vs 41 percent, respectively). Thrombo-

should be observed during the infusion and for

cytopenia (12.9 percent) and transaminase

at least 30 minutes after the infusion. [KADCY-

elevation (4.3 percent with elevated aspartate

LA Full Prescribing Information]

aminotransferase and 2.9 percent with elevated ALT) were the most common serious

Place in guidelines

adverse events. Both adverse effects can be

In the European Society for Medical On-

managed in most patients by dose reduction.

cology (ESMO) consensus guidelines for ad-

In the EMILIA trial, only 10 patients discontin-

vanced breast cancer, T-DM1 is recommended

ued treatment due to thrombocytopenia. [New

after first-line trastuzumab-based therapy in

Engl J Med 2012;367:1783-1791]

patients with HER2-positive advanced breast

Cardiac toxicity is a well-known adverse

cancer. T-DM1 provides superior efficacy to

event of trastuzumab. In the EMILIA study, only

other HER2-based therapies in the second-line

O c to b e r 2 01 4

d r u g p r ofi l e

14

setting. As T-DM1 has shown significant overall

of HER2-positive metastatic breast cancer. This

survival (OS) benefits, it is the preferred thera-

treatment uses HER2 as a biomarker to target

py for patients who have progressed through

toxic chemotherapy directly into cancer cells.

at least one line of trastuzumab-based therapy.

By targeting delivery, T-DM1 improves the ther-

[Ann Oncol 2014; ePub prior to print]

apeutic window of the cytotoxic component.

The American Society of Clinical Oncology

T-DM1 activity relies on continued overexpres-

(ASCO) recommends the use of T-DM1 for sec-

sion of HER2, which has been shown to persist

ond-line treatment of HER-2 positive advanced

on treatment-resistant breast cancer cells.

breast cancer. In the third-line setting, ASCO

T-DM1 is generally well tolerated and has

recommends other HER-2 targeted therapy

been shown in randomized trials to be more ef-

combinations, T-DM1 or pertuzumab (if these

fective than standard chemotherapy added to

have not been previously used). [J Clin Oncol

HER2-targeted drugs.

2014;32:2078-2099]

Cardiac event rates related to T-DM1 will

Similarly, the National Comprehensive Can-

be further addressed in an ongoing large first-

cer Network (NCCN) also recommends T-DM1

line study (MARIANNE**), where it is being

as the preferred option for treatment of patients

directly compared with a trastuzumab-based

with HER2-positivie metastatic breast cancer

regimen.

who have previously received a trastuzumab-based regimen. [NCCN Clinical Practice

*EMILIA: Trastuzumab Emtansine for HER2-Positive Ad-

Guidelines in Oncology: Breast Cancer (Ver-

vanced Breast Cancer

sion 3:2014);2014]

**MARIANNE: A Study of Trastuzumab Emtansine (TDM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastu-

Summary and conclusions

T-DM1 is a novel approach for the treatment

zumab [Herceptin] Plus a Taxane in Patients with Metastatic Breast Cancer

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

16

European Society of Cardiology (ESC) Congress 2014,

August 30 September 3, Barcelona, Spain

Iron deficiency an attractive

therapeutic target in HF
CHRISTINA LAU

intravenous iron, given as ferric carboxymaltose

solution (FCM) (n=152), or a normal saline place-

atients with symptomatic heart failure (HF)

bo (n=152) for 52 weeks. The primary endpoint

and iron deficiency can experience signifi-

was change in 6-minute walking test (6MWT) dis-

cant and sustained improvements in functional

tance at 24 weeks.

capacity, symptoms and quality of life (QoL) as

well as a reduced risk of hospitalization for worsening HF after receiving just one or two doses of
intravenous iron supplement.
These results, from the CONFIRM-HF* trial,
suggest correction of iron deficiency to be an attractive therapeutic target in HF. [Eur Heart J 2014,
e-pub 31 Aug, doi: 10.1093/eurheartj/ehu385]

The risk of hospitalization due

to worsening HF was reduced
significantly by 61 percent with
FCM vs placebo (10 vs 32 events;
p=0.009) 

Iron deficiency affects about 50 percent of HF

patients, and has been associated with impaired
functional capacity, poor QoL and increased mor-

In the FCM arm, the median total dose of

tality irrespective of the presence of anemia. But

iron was 1,500 mg. More than 75 percent of the

the problem has been under-recognized, said

patients required a maximum of two FCM injec-

CONFIRM-HF investigator Professor Piotr Poni-

tions, reported Ponikowski.

kowski from the Medical University in Wroclaw,

Poland.

At 24 weeks, patients in the FCM arm improved on the 6MWT by 18 meters, while those

The double-blind, placebo-controlled trial in-

in the placebo arm had a decrease of 16 meters.

cluded 304 patients with stable, symptomatic

The 33-meter difference compared with placebo

HF (New York Heart Association [NYHA] func-

was significant [p=0.002], he said. Importantly,

tional class II/III, left ventricular ejection fraction

improvement in 6MWT distance was seen across

45 percent) and iron deficiency (serum ferritin

all subgroups, including in patients with and with-

level <100 ng/mL or 100-300 ng/mL if transfer-

out anemia.

ring saturation <20 percent) from nine European

At 36 and 52 weeks, FCM-treated patients

countries. Patients were randomized to receive

completed an additional 42 and 36 meters on

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

17

the 6MWT, respectively, compared with placebo

ment from week 12, NYHA functional class from

(both p<0.001).

week 24, as well as fatigue and QoL.

The magnitude of effect of FCM on 6MWT

However, mortality was similar between the

distance is robust and clinically meaningful. Simi-

two treatment arms (12 events for FCM vs 14

lar effects have been seen only with cardiac re-

events for placebo; hazard ratio, 0.89; p=0.77).

synchronization therapy in previous international

This suggests a 1-year follow-up may not be

trials, said Ponikowski.

long enough to detect differences in mortality,

The risk of hospitalization due to worsening

Ponikowski noted.

HF was reduced significantly by 61 percent with

FCM vs placebo (10 vs 32 events; p=0.009). Pa-

*CONFIRM-HF: Ferric Carboxymaltose Evaluation on Per-

tients treated with FCM also showed significant

formance in Patients with Iron Deficiency in Combination

improvements in self-reported global assess-

with Chronic Heart Failure.

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

18

European Society of Cardiology (ESC) Congress 2014,

August 30 September 3, Barcelona, Spain

Complete revascularization trumps

targeted unblocking of culprit lesion
in MI
Radha Chitale

findings should suggest strongly that all lesions

be treated before the patient is discharged.

multi-pronged revascularization effort in

The trial randomized patients presenting with

significantly blocked arteries was superior

heart attack to complete revascularization of

to a targeted approach focusing only on the

the IRA and non-IRAs if they were significantly

culprit lesion in patients being treated for heart

blocked (n=150) or IRA revascularization only

attack, according to the results of the Complete

(n=146) prior to PCI. Patients had no prior his-

versus Lesion only Primary-PCI Trial (CvLPRIT).

tory of coronary artery bypass surgery.

The primary endpoint, a composite of total

mortality, recurrent myocardial infarction (MI),
heart failure, and ischemia-driven revascularization at 12 months, occurred in 10 percent of
complete revascularization patients and in 21.2

Current guidelines ... recommend

treating the IRA only, but the
results of our study demonstrate

percent of infarct-related artery (IRA) only pa-

a highly significant benefit

tients (hazard ratio [HR] 0.45; p=0.009).

with a strategy of complete

Until now, there have been conflicting data

regarding the optimal management of patients

revascularization instead 

who, whilst undergoing primary percutaneous

coronary intervention (P-PCI) after MI, are also

Primary endpoint outcomes were significant-

found to have lesions in their non-IRA, said

ly better in the complete revascularization group

lead study investigator Dr. Anthony Gershlick

and this became evident within 30 days of PCI.

from University Hospitals of Leicester NHS Trust,

Glenfield Hospital, in Leicester, England.

Gershlick said doctors should consider treating non-IRAs at the time of PCI as opposed to

Current guidelines ... recommend treating

scheduling subsequent revascularizations at a

the IRA only, but the results of our study demon-

later date, given the number of events that oc-

strate a highly significant benefit with a strategy

curred within a month. Of the 146 patients ran-

of complete revascularization instead. These

domized to IRA only, 31 reached the primary

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

19

endpoint at 30 days compared with 15 of the 150

Hamilton, Ontario, Canada, commenting on the

complete revascularization patients (p<0.009).

study.

CvLPRIT demonstrated 55 percent reduc-

The guideline recommendations are based

tion in MACE [major adverse cardiac events] in

on a large meta-analysis of observational data

those patients presenting for P-PCI when non-

on over 30,000 patients that favor IRA revascu-

IRA artery is also treated on index admission

larization (HR, 1.35; p<0.00001) over complete

with no adverse safety signal, Gershlick said.

revascularization (HR, 0.35; p<0.0001), he not-

However, it is unlikely that the CvLPRIT results will immediately change practice.
There is agreement on both sides of the At-

ed, whereas the CvLPRIT sample was too small

to detect differences in death or MI. [Am Heart J
2014;167:1-14.e]

lantic in the guideline documents that [same-

The important question is was there a sig-

sitting PCI] is a potentially harmful procedure,

nificant hazard with doing revascularization at a

said Dr. Shamir Mehta of McMaster University in

later time.

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

20

European Society of Cardiology (ESC) Congress 2014,

August 30 September 3, Barcelona, Spain

Rosuvastatin may be better option

than atorvastatin for diabetics
Chuah Su Ping

At 3 months, the researchers noted that LDLcholesterol reduction was significantly greater

ata from the LISTEN* trial have indicated

in the rosuvastatin group than in the atorvas-

that rosuvastatin may have an initially more

tatin group (-39.38 vs -36.39 percent mg/dL;

favorable effect on glucose levels compared to

p=0.0106). The initial increase in blood glucose

atorvastatin.

was statistically more pronounced (p=0.0104)

There is currently concern that statin treat-

in the atorvastatin group (121.4 and 126.0 mg/

ment may exert diabetogenic effects, favoring

dL at 3 and 6 months, respectively) compared

the development of newer-onset type 2 diabetes. Such effects appear greater in patients receiving high-dose statins and in obese patients

A
 statins impact on glucose

with metabolic syndrome at high cardiovascular

metabolism should also be

risk, said Professor Hisao Ogawa of the Department of Cardiovascular Medicine at Kumamoto

considered along with its

University Graduate School of Medical Scienc-

cholesterol-lowering potency

es, Kumamoto, Kyushu, Japan.

when making treatment choices

Ogawa, who is one of the LISTEN study investigators, noted that the study was carried out
to examine the effects of statins on both lipid

for diabetic patients with high

cholesterol 

and glucose control in Japanese patients with

diabetes. The study cohort comprised middle-

with the rosuvastatin group (118.8 and 122.9

aged male and female type 2 diabetic subjects,

mg/dL at 3 and 6 months, respectively). The

who had well-controlled glycemia (HbA1c<7

intensification of diabetic treatments, noted

percent) with a moderate degree of dyslipid-

Ogawa, was significantly less frequent in the

emia and a low incidence of diabetic complica-

rosuvastatin group than in the atorvastatin

tions (<10 percent incidence of microangiopa-

group. At the end of the study, both groups had

thy). Patients were randomized to rosuvastatin 5

a reduction in non-HDL cholesterol, with non-

mg daily or atorvastatin 10 mg daily for a year.

statistically significant difference between the

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

21

rosuvastatin and atorvastatin groups (-32.86

ol, said Ogawa. Our results suggest rosuvas-

and -31.01 percent, respectively). Similarly, the

tatin might be [preferable] to atorvastatin due to

reduction in LDL cholesterol was not signifi-

its different influence on glucose levels. However,

cantly different between the two groups (-34.79

further prospective studies are required to confirm

and -32.78 percent, respectively) at 12 months.

the differences in the effects on diabetes among

A statins impact on glucose metabolism

statins.

should also be considered along with its cholesterol-lowering potency when making treatment

*LISTEN: Lipid Lowering with Highly Potent Statins in

choices for diabetic patients with high cholester-

Hyperlipidemia with Type 2 Diabetes Patients.

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

22

European Society of Cardiology (ESC) Congress 2014,

August 30 September 3, Barcelona, Spain

Vagus nerve stimulation does

not improve cardiac function in
HF patients
Chuah Su Ping

Both groups had comparable changes from

baseline in the primary endpoint of left ventricu-

he results of the NECTAR-HF* trial have

lar end-systolic dimension (LVESD) as well as

revealed that stimulating the vagus nerve

in the secondary endpoints of exercise capacity,

does not improve cardiac function in heart fail-

levels of HF serum biomarker N-terminal prohor-

ure (HF) patients.

mone brain natriuretic peptide, and other echo-

The study is the first randomized controlled

cardiographic parameters.

trial designed to evaluate the safety and efficacy

of right-sided vagus nerve stimulation (VNS) in
severe HF patients with severe left ventricular

Patients in the NECTAR-HF trial

(LV) systolic dysfunction despite medical ther-

were relatively well-managed on

apy.

medical therapy alone, making

Ninety-six HF patients from 24 centers across

Western Europe were randomized to an active
VNS device or a device that was implanted
but not turned on (control) and followed for 6

them perhaps not the best

candidates to show a strong
benefit of VNS 

months. [Eur Heart J 2014. pii:ehu345]

Although robust pre-clinical data showed

We noted, however, statistically significant

the benefit of VNS, NECTAR-HF failed to dem-

improvements in the QoL measures with VNS

onstrate a successful clinical translation of VNS

treatment compared with controls as measured

therapy to the primary endpoint of cardiac re-

by the Minnesota Living with Heart Failure Ques-

modelling, said study author Dr. Faiez Zannad,

tionnaire and the Short Form 36 Health Survey,

head of the Division of Heart Failure and Hyper-

said Zannad.

tension at lInstitut Lorrain du Coeur et des Vais-

Additionally, 62 percent of patients in the VNS

seaux Louis Mathieu in Vandoeuvre-ls-Nancy,

group had an improvement of at least one point

France. This failure to show a cardiac benefit

from baseline in their New York Heart Associa-

was unexpected.

tion functional classification compared with only

45 percent of control patients (p=0.0320).

O c to b e r 2 01 4

CO N F ERE N CE COV ERAGE

23

cal therapy alone, making them perhaps not the

The safety profile for this application of VNS

best candidates to show a strong benefit of VNS.

appeared acceptable, with an overall infection

Third, the 6-month study period may have been

rate of 7.4 percent, which is comparable to that

too short to detect changes in cardiac function.

in patients implanted with a VNS system for the

He also noted that it is possible that those

treatment of epilepsy, said Zannad.

in the active treatment group were able to feel

Zannad offered a number of possible explana-

the sensation of stimulation, thus they could

tions for NECTAR-HFs negative findings. Data

have been vulnerable to a placebo effect. For

from epilepsy VNS studies show that higher-

this reason, the higher QoL scores among

amplitude dosing might be more effective, but

the VNS patients should be interpreted with

it is often not possible because it causes patient

caution.

discomfort. Second, patients in the NECTARHF trial were relatively well-managed on medi-

*NECTAR-HF: Neural Cardiac Therapy for Heart Failure

O c to b e r 2 01 4

RES E A RCH REV IEWS

25

Korean red ginseng beneficial for women with premenstrual

syndrome

orean red ginseng (KRG), which is processed from raw ginseng, improves the

quality of life of women by ameliorating oxidative stress induced by exposure to endocrinedisrupting bisphenol A (BPA), according to a
recent study.
The single-blind, randomized clinical trial investigated the efficacy and safety of KRG in 22
healthy non-smoking women aged 21 to 30 who
experienced premenstrual symptoms such as
menstrual pain or irregularity. The women were

duced urinary BPA and MDA levels as well as

randomized to receive KRG 2.7 g/day or place-

symptoms of menstrual irregularity, menstrual

bo after meals for 2 weeks. Analyses were based

pain, and constipation (p<0.05). The reduc-

on levels of BPA and malondialdehyde (MDA), a

tion in urinary BPA was observed from day 4.

biomarker of oxidative stress, in urinary samples

According to typology, the SoEum type (Lesser

collected before breakfast on days 0, 4, 8, and

Yin) experienced significantly greater allevia-

14, as well as responses to a questionnaire on

tions of insomnia, flushing, perspiration, and ap-

gynecologic complaints collected at the same

petite than the other types.

four time points. Individual variations in susceptibility to KRG were determined using the tra-

Yang M et al. Effects of Korean red ginseng (Panax Gin-

ditional Korean Sasang Typologythe Sasang

seng Meyer) on bisphenol A exposure and gynaecologic

Constituent Classification (QSCC II).

complaints: single blind, randomized clinical trial of ef-

Supplementation with KRG significantly re-

ficacy and safety. BMC Compl Altern Med 2014; 14:265.

O c to b e r 2 01 4

RES E A RCH REV IEWS

26

PAS 400 supplementation normalizes response to acute stress

n chronically stressed subjects, oral supple-

riod was followed by an acute stress test (Trier

mentation with a phosphatidylserine (PS)/

Social Stress TestTSST).

phosphatidic acid (PA) complex normalizes

Daily supplementation with PAS 400 effec-

the hyper-responsivity of the hypothalamus-

tively normalized adrenocorticotropic hormone

pituitary-adrenal axis (HPAA) to an acute

(p=0.010), salivary (p=0.049), and serum cor-

stressor, according to a multinational group of

tisol (p=0.035) responses to the TSST in sub-

researchers.

jects with chronically high, but not chronically

The effects of oral supplementation with a

low, stress levels. PAS 200 supplementation ef-

complex containing 400 mg/day PS and 400

fects did not differ significantly from those of

mg/day PA (PAS 400) on endocrine response

the placebo (all p>0.05). In addition, supple-

to a psychosocial stressor were compared with

mentation did not have any significant effects

those of a 200 mg/day PS/200 mg/day PA com-

on heart rate, pulse transit time, or psychologi-

plex (PAS 200) in 75 healthy non-smoking male

cal stress response (all p>0.05)

volunteers aged 20 to 45 in a double-blind, placebo-controlled study. The men were stratified

Hellhammer J et al. A soy-based phosphatidylser-

by chronic stress level (measured with the Trier

ine/ phosphatidic acid complex (PAS) normalizes the

Inventory for Chronic Stress [TICS]) and ran-

stress reactivity of hypothalamus-pituitary-adrenal-axis

domly allocated to placebo (n=25), PAS 200

in chronically stressed male subjects: a randomized,

(n=25), or PAS 400 (n=25) supplementation

placebo-controlled study. Lipids Health Dis 2014; 13:121.

for 42 days. The 6-week supplementation pe-

doi:10.1186/1476-511X-13-121.

O c to b e r 2 01 4

RES E A RCH REV IEWS

27

Acute air pollutant exposure not linked to short-term

arrhythmia risk

he association between exposure to air

pollution and the risk of cardiovascular

morbidity and mortality has been explored in

a number of epidemiological studies. Since
air pollutants can influence cardiac autonomic
tone and reduce heart rate variability, these trials may increase the risk of cardiac arrhythmias,
particularly in susceptible patients. However, a
recent investigation analyzing the incidence of
cardiac arrhythmias during and after controlled
exposure to air pollutants did not find any such
effect in healthy volunteers or patients with cor-

air pollution in either the healthy volunteers or

onary heart disease (CHD).

the patients with CHD.

Data from 13 consecutive double-blind,

The researchers concluded that research

randomized, crossover studies performed be-

employing these comparative techniques does

tween 2004 and 2013 that collectively included

not unnecessarily increase the short-term risk of

282 participants (140 healthy volunteers, 142

arrhythmia and should therefore be continued

patients with stable CHD) with continuous elec-

given the potential benefits to society and the

trocardiograms were analyzed.

use of these data for informing environmental

The incidence of any type of cardiac arrhyth-

and public health policy decisions.

mia was not increased during or after exposure

to dilute diesel exhaust, wood smoke, ozone,

Langrish JP et al. Controlled exposures to air pollutants

concentrated ambient particles, engineered

and risk of cardiac arrhythmia. Environ Health Perspect

carbon nanoparticles, or high ambient levels of

2014; 122:747753.

O c to b e r 2 01 4

RES E A RCH REV IEWS

28

Fluoxetine may influence the pathogenesis of

brain metastasis in breast cancer

ntidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are com-

monly prescribed to breast cancer patients, but

these agents are neuroactive and may influence the pathogenesis of brain metastasis, according to the findings of a recent animal study.
The effect of fluoxetine, a SSRI, on the development of brain metastatic breast cancer
was investigated in Nu/Nu mice intracardially
injected with MDA-MB-231BR cells.
The number of brain metastases was found
to be increased by 52 percent by fluoxetine administration. Moreover, the effect was accom-

screening of neuroactive drugs is necessary to

panied by increased permeability of the blood-

determine whether they have the potential to

brain barrier, pro-inflammatory changes in

increase the development of brain metastasis

the brain, and glial activation, suggesting that

in breast cancer patients.

fluoxetine promotes the entry of cancer cells

into the brain by modifying the function of the

Shapovalov Y et al. Fluoxetine modulates breast cancer

blood-brain barrier.

metastasis to the brain in a murine model. BMC Cancer

The researchers conclude that careful

2014 Aug 16;14(1):598. [Epub ahead of print].

O c to b e r 2 01 4

RES E A RCH REV IEWS

29

Infants at high risk of developing autism show low functional

EEG connectivity at 12 months

ompared with low-risk individuals, infants

age 12 months functional connectivity was sig-

who have a high risk of developing autism

nificantly lower among the high-risk infants.

spectrum disorders show low levels of func-

Moreover, functional connectivity was lowest

tional connectivity on electroencephalography

among high-risk infants who were subsequent-

(EEG) studies conducted at age 12 months, ac-

ly diagnosed with an autism spectrum disor-

cording to a recent study performed in the US.

der compared with both low-risk infants and

The researchers tested infants at both high

high-risk infants who did not develop any such

(n=28) and low (n=26) risk of developing an

disorder.

autism spectrum disorder by comparing EEG

The researchers comment that these findings

measurements of intrahemispheric linear co-

indicate that functional connectivity appears to

herence between anterior and posterior sites

be related to genetic vulnerability to autism spec-

(a measure of neural functional connectivity) at

trum disorders with differences in neural integra-

6 and 12 months of age while the infants were

tion emerging during the first year of life.

listening to speech sounds. High risk was defined as having an older sibling diagnosed with

Righi G et al. Functional connectivity in the first year of

an autism spectrum disorder.

life in infants at risk for autism spectrum disorder: an EEG

Although there was no difference between

low- and high-risk infants at age 6 months, at

study. PLoS ONE 2014; 9(8): e105176. doi:10.1371/journal.

pone.0105176.

O c to b e r 2 01 4

RES E A RCH REV IEWS

30

Chlorinated solvent exposure increases breast cancer risk

reast cancer risk is significantly increased

among women employed in the electrical

manufacturing industry who are exposed to

chlorinated solvents, particularly trichloroeythlene, say Italy-based researchers.
Their nested case-control study investigated
possible associations between chlorinated solvent exposure and breast cancer risk among a
cohort of women employed in a large electrical manufacturing plant in Lombardy, Milan. All
histologically confirmed cases of female breast
cancer during 20022009 in individuals aged
35 to 69 years who were resident in Lombar-

significantly increased among women who

dy and had worked for at least 1 year in the

had been exposed to chlorinated solvents,

factory from 1974 to 2005 were selected from

particularly trichloroethylene (OR 1.65, 95%

hospital discharge records (n=76). These were

CI, 1.042.62). Moreover, women who had

then compared with randomly sampled control

been exposed for at least 10 years had a

women who were resident in Lombardy as of

two-fold increased risk of developing breast

December 31, 2005 and had worked in the fac-

cancer (OR 2.10, 95% CI 1.213.66).

tory for 1 year between 1974 and 2005, but did

not develop breast cancer (n=140).
The researchers found that odds ratios
(ORs) adjusted for known risk factors were

Oddone E et al. Female breast cancer and electrical manufacturing: results of a nested case-control study. J Occup
Health 2014; Aug 28. [Epub ahead of print].

O c to b e r 2 01 4

RES E A RCH REV IEWS

31

Excessive salt consumption in pre-hypertensive women linked

to processed foods

xcessive salt consumption is a public

ments and questionnaire responses relating to

health problem that can lead to hyperten-

demographic characteristics and dietary habits

sion, stroke, and renal disease. Although nu-

were also collected.

merous methods for reducing salt consumption

A total of 82.1 percent of the women had a

have been proposed, controversy remains over

salt intake above the 5 g/day recommended by

whether sodium intake is most affected by the

the WHO the average salt intake from urinary

consumption of processed foods, the discre-

excretion was estimated to be 7.8 3.2 g/day.

tionary use of salt in cooking, or both. Now, a

Soup (21.6 percent), rice and noodles (13.5 per-

study in Hong Kong has found that processed

cent), baked cereals (12.3 percent), salted/pre-

foods such as soup and rice and noodles are

served foods (10.8 percent), Chinese dim sum

the greatest sources of salt among postmeno-

(10.2 percent), and seafood (10.1 percent) were

pausal women with prehypertension.

identified as the major sources of sodium intake.

In the cross-sectional study, sodium intake

The researchers suggest that a potential

was investigated among 655 Chinese post-

strategy for reducing sodium intake would be to

menopausal women aged 48 to 70 with prehy-

reduce sodium levels in soup and to encourage

pertension who were screened for a randomized

an increase in fruit intake.

controlled trial. The women provided 24-hour

urine samples for the measurement of sodium,

Liu Z-M et al. Urinary sodium excretion and dietary sources of

potassium, and creatinine, as well as 3-day di-

sodium intake in Chinese postmenopausal women with prehyper-

etary records. Data on anthropometric measure-

tension. PLoS ONE 2014; 9(8): e104018.

october

15th World Congress on Pain

6/10/2014 to 11/10/2014
Location: Buenos Aires, Argentina
Info: IASP Secretariat
Tel: (1) 202 524 5300
Fax: (1) 202 524 5301
Email: IASPdesk@iasp-pain.org
Website: www.iasp-pain.org/
Meetings/WorldCongress
Asia Pacific Association of
Pediatric Allergy, Respirology and
Immunology (APAPARI) Congress
2014
8/10/14 to 10/10/14
Yogyakarta, Indonesia
Info: APAPARI
Tel: +62 822 2632 8826
Email: admin@apapari2014
Website: www.apapari2014.com
Diabetes Asia 2014 Conference
16/10/2014 to 19/10/2014
Location: Kuala Lumpur, Malaysia
Info: NADI
Tel: (60) 3 7876 1676, (60) 3 7876
1677
Fax: (60) 3 7876 1679
Email: enquiry@nadidiabetes.com.
my
Website: www.diabetesmalaysia.com.
my
9th World Stroke Congress
22/10/2014 to 25/10/2014
Location: Istanbul, Turkey
Info: Secretariat
Tel: (41) 22 908 0488
Fax: (41) 22 906 9140
Email: WSC2014_reg@kenes.com
Website: www2.kenes.com/
stroke2014
NO V E M BER

2014 IASLC Asia Pacific Lung

Cancer Conference
6/11/14 to 8/11/14
Kuala Lumpur, Malaysia
Info: International Association for the
Study of Lung Cancer
Email: info@aplcc2014.com
Websie: www.iaslc.org

O c to b e r 2 01 4

19th Congress of the Asian Pacific

Society of Respirology
13/11/14 to 16/11/14
Bali, Indonesia
Info: Asian Pacific Society of
Respirology
Email: secretariat@apsr2014.org
Website: www.apsr2014.org
8th Congress of the Asian Society
Against Dementia
14/11/2014 to 16/11/2014
Location: Colombo, Sri Lanka
Info: A/Prof Christopher Chen,
Department of Pharmacology, Yong
Loo Lin School of Medicine, National
University of Singapore
Tel: (65) 6516 3264
Fax: (65) 6773 0579
Email: phccclh@nus.edu.sg
Website: www.asiandementia.org
IOF Regionals 5th Asia-Pacific
Osteoporosis Meeting
14/11/2104 to 16/11/2014
Location: Taipei, Taiwan
Info: IOF
Tel: (41) 22 994 0100
Fax: (41) 22 994 0101
Email: taipei2014@iofbonehealth.org
Website: www.iofbonehealth.org/
taipei-2014
10th International Diabetes
Federation-Western Pacific Region
(IDF-WPR) Congress and 6th
Asian Association for the Study of
Diabetes Scientific Meeting
21/11/14 to 24/11/14
Singapore
Info: IDF-WPR/AASD
Tel: +65 6411 6684
Email: secretariat@idfwpr2014.org
Website: www.idfwpr2014.org
Asian Pacific Digestive Week 2014
22/11/2014 to 25/11/2014
Location: Bali, Indonesia
Info: APDW2014 Congress
Secretariat
Tel: (65) 6346 4402
Fax: (65) 6346 4403
Email: secretariat@apdw2014.org
Website: www.apdw2014.org

D E C E M BER

C A LEN DA R

32

20th World Congress on

Controversies in Obstetrics,
Gynaecology and Infertility (COGI)
4/12/2014 to 7/12/2014
Location: Paris, France
Info: COGI Secretariat
Tel: (972) 73 706 6950
Fax: (972) 3 725 6266
Email: cogi@congressmed.com
Website: www.congressmed.com/
cogi/
12th Asian Congress of Urology
(ACU)
5/12/2014 to 9/12/2014
Location: Kish Island, Iran
Info: Secretariat
Tel: (971) 4 4218996
Fax: (971) 4 4218838
Email: Plus@InfoPlusEvents.com
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u pc o m i n g
International Conference on
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16/1/15 to 18/1/15
Phnom Penh, Cambodia
Info: Govt. Gandhi Memorial Science
College
Email: geo_stv_goss@hotmail.com
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9th Asia Pacific Conference on
Clinical Nutrition (APCCN)
26/1/2015 to 29/1/2015
Location: Kuala Lumpur, Malaysia
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Tel: (603) 2162 0566
Fax: (603) 2161 6560
Email: apccn2015@console.com.my
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14th World Congress on Public
Health
11/2/15 to 15/2/15
Kolkata, India
Phone: +91 124 463 6713
Email: info@14wcph.org
Website: http://www.14wcph.org/

O c to b e r 2 01 4

humor

33

Ah! Here you are!

Dont be frightened! Its just a tapeworm that

turned out to be slightly larger than we thought!

Its the latest in high tech

coffins, Larry. A Samsung 4K
Ultra HD LED HDTV and it
comes with a remote control!

Are you almost done with the sports section?

I dont know about you but

Ive a bad feeling about this!

He definitely has asthma. I think

he should give up smoking!

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

Professor
Peter Ebeling

Professor
Serge Ferrari

Dr Edith Lau

Professor Bess
Dawson-Hughes

Widespread vitamin D
deficiency and low calcium
levels in Asians

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

Treatment plans for

post-menopausal women
with osteoporosis

How aging contributes to

sarcopenia and impaired
muscle function in the
elderly

How low levels of awareness

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

MIMS Video Series features

interviews with leading experts

For A 5-minute Update

Go to www.mims.asia/video_series

SCAN TO WATCH VIDEO

Brought to you by MIMS

Publisher

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