NEWS & INSIGHTS

MARCH 2016
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1

Targeting insulin
resistance may prevent
CV events after stroke

10

FORUM

NEWS

World needs
new diagnostics,
replacement
antimicrobials
and more vaccines

Cheaper, nonsurgical
procedure could help
obese patients
lose weight

NEWS

NEWS

Chinese diet
still too high in salt
and sodium

Eluxadoline offers
symptom relief from
IBS with diarrhoea

15/10/15

10:16 am


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MARCH 2016 • 2

Targeting insulin resistance may
prevent CV events after stroke
ELVIRA MANZANO

I

mproving insulin sensitivity in patients who

have had a recent stroke may lower the risk

of heart attack or a second stroke, according
to the IRIS* trial, showing for the first time that
targeting insulin resistance is effective at reducing cardiovascular events.
“This represents a new opportunity for keep-

infarction (MI) compared with 11.8 percent of

ing people healthy after a stroke or a transient

those receiving placebo (HR, 0.76; p=0.007).

ischaemic attack [TIA] and for new drug devel-

In addition, fewer patients in the pioglitazone

opment,” said lead study author Dr. Walter Ker-

group progressed to diabetes (3.8 versus 7.7

nan, professor of medicine at the Yale University

percent for placebo; p<0.001).

in New Haven, Connecticut, US. The findings

However, patients on pioglitazone had more

also put a premium on insulin resistance as a


weight gain (p<0.001), oedema (p<0.001), and

new target for secondary stroke prevention.

bone fractures requiring surgery or hospitaliza-

The IRIS trial included 3,876 patients aged

tion (p=0.003).

40 or older without diabetes but who had insulin

The findings suggest that treatment with pio-

resistance (homeostasis model assessment of

glitazone for about 5 years could prevent three

insulin resistance [HOMA-IR] index, >3.0) and

strokes or MI in 100 patients. However, these

a stroke or TIA in the 6 months prior to study

benefits should be balanced with potential risks,

enrolment, randomized to receive pioglitazone

including serious bone fractures, which would


45 mg daily or a matching placebo. [N Engl J

be expected in two patients, said the authors.

Med 2016;doi: 10.1056/NEJMoa1506930]

“More research is warranted to determine the

Pioglitazone of the thiazolidinedione class

mechanisms by which pioglitazone decreases

of peroxisome proliferator–activated receptor γ

risk for stroke and heart attack and increases

(PPARγ) agonists is approved in combination

bone fracture risk, with the hope of develop-

with other blood glucose-lowering agents for

ing strategies that maximize benefit and mini-

the treatment of type 2 diabetes (T2D).

mize serious side effects in our patients,” said

Over a median follow-up of 4.8 years, 9 per-


Kernan.

cent of patients taking pioglitazone experienced

In an accompanying commentary, Dr. Clay

the primary outcome of stroke or myocardial

Semenkovich from the Washington University in


MARCH 2016 • 3

St. Louis, St. Louis, Missouri, US said the find-

those with substantial deficits. [N Engl J Med

ings may “tempt clinicians to rush to prescribe

2016;doi:10.1056/NEJMe1600962]

pioglitazone.”

Nevertheless, pioglitazone represents a po-

However, there are a number of caveats

tentially important therapy for the secondary pre-


which concern the validity of the results. First,

vention of vascular events in appropriately se-

patients in the IRIS trial had no heart failure and

lected patients with CVD, said Semenkovich.

little neurologic impairment, said Semenkovich.
Response to pioglitazone may be different for

*IRIS: Insulin Resistance Intervention after Stroke trial

Music therapy benefits COPD
patients undergoing pulmonary
rehabilitation
PEARL TOH

M

usic can benefit not just your mind, but
also your lungs. Music therapy combined

with standard pulmonary rehabilitation (PR) improved respiratory symptoms, psychological
well-being, and quality of life in patients with
chronic obstructive pulmonary disease (COPD)
and other chronic respiratory disorders, com-

no adverse side effects, and improves com-


pared with patients receiving PR alone, the AIR*

munication between patients, families, and

study showed. [Respir Med 2015;109:1532-

medical staff,” Canga said. “Therefore, mu-

1539]

sic therapy has an impressive profile of 

Lead author Mr. Bernardo Canga, a music
therapist and researcher from the Louis Arm-

treatment adherence, which is vital in the
recovery process.”

strong Center for Music and Medicine at Mount

Study participants given music therapy in addi-

Sinai Beth Israel (MSBI) hospital, New York,

tion to PR (treatment group) demonstrated fewer

New York, US, believes music therapy has a

depressive symptoms (Least-Square [LS] mean


huge impact on the quality of care provided.

-0.2), compared to control group receiving PR

“Music

therapy is

cost-effective,

has

alone (LS mean 1.3, p=0.007).


MARCH 2016 • 4

Health-related Quality of Life (HRQL), as mea-

apy administered by certified music therapists for

sured by Chronic Respiratory Questionnaire

6 weeks. The music therapy included live music,

Self-Reported (CRQ-SR), improved in  the treat-

visualizations, singing, and wind instrument play-

ment group in the four criteria evaluated: dys-


ing, which incorporated the patients’ preferred

pnoea (LS mean 0.5, p=0.01), fatigue (LS mean

music styles.

0.3, p=0.01), emotional function (LS mean 0.3,

Canga said allowing patients to choose

p=0.005), and mastery (LS mean 0.5, p=0.06),

familiar music encourages self-expression,

compared with controls. Additionally, music ther-

increases engagement in therapeutic activi-

apy significantly improved perceived dyspnoea

ties, and provides an opportunity to cope with

in patients, measured by a Dyspnoea Visual An-

the challenges of a chronic condition.

alogue Scale (VAS), especially in week 5 and 6

“Our study is the first to our knowledge that


of the study (p<0.001), compared with controls.

incorporates a multimodal intervention adjunct

“We hope that our results reinforce a com-

to standard PR using certified music therapists.”

prehensive foundation for the establishment of

Expanding on the current study, the Louis Arm-

music therapy as part of PR care... and [it will

strong Center for Music and Medicine is currently

become] more commonly used in clinical set-

using music therapy to enhance the breathing

tings,” said Canga.

capacity and quality of life of children and teens

A total of 68 participants (mean age 70.1

with asthma under the Asthma Initiative Program.

years), with moderate to severe GOLD stage II-


Canga said his team would like to focus on the

IV lung diseases and other conditions causing

effect of music therapy intervention specifically on

chronic airflow limitations, completed the study.

pulmonary function in future study.

Participants were randomly assigned to control group, receiving PR alone, or the treatment

*AIR: Advances in Respiration -Music therapy in the treatment of

group, who received PR plus psycho-music ther-

chronic pulmonary disease


MARCH 2016 • FO R U M • 5

World needs new diagnostics,
replacement antimicrobials and more
vaccines to prevent infections
Excerpted from a speech by Dr. Margaret Chan, director-general of the World Health
Organization, during the European Union Ministerial Conference on Antimicrobial
Resistance held in Amsterdam, the Netherlands recently.

F


or more than a decade, the European Union
has been a world leader in the struggle to

combat antimicrobial resistance (AMR). This is
readily apparent in the number of policies, directives, technical reports, strategies, and regulatory decisions designed to reduce antibiotic
consumption, in humans and animals, ensure
the prudent use of these fragile medicines, and
protect specific agents that are critically important for human medicine.
You have moved forward in remarkable ways,
as reflected in several EU-wide networks for

demand for meat as household incomes im-

surveillance of both resistance and consump-

prove. This growing demand, especially when

tion, and for susceptibility testing.

met by intensive farming practices, contributes

Significantly, the EU-wide ban on the use of
antibiotics as growth promoters in animal feed
has not weakened the region’s leading position
in global food production.

to the massive use of antibiotics in livestock
production.
Worldwide, we need to insist that risks to human health guide the prudent use of antibiotics


Compelling evidence shows that resistance

in food production. The WHO list of critically im-

is driven by the total volume of antibiotics used,

portant antimicrobials for human medicine pro-

also in food production. Worldwide, antibiotic

vides a tool for doing so.

use in humans, animals, and agriculture is still

The world certainly needs to feed its nearly

increasing, despite effective reductions in some

7.4 billion people, but not in ways that cause

countries.

our mainstay antimicrobials to fail. Combatting

In several large emerging economies, studies have consistently documented a rise in the

antimicrobial resistance, in line with the global
action plan, is a matter of utmost urgency.



MARCH 2016 • FO R U M • 6

The health sector, acting alone, cannot possi-

Colistin is a 50-year-old antibiotic that was

bly contain a threat of this magnitude. We need

shelved in the 1970s because of its toxic effects

to work together with partners. Conferences like

on the kidneys. It was brought back into clinical

this one can move a broad agenda forward as a

use when all newer antibiotics began to fail.

model for the rest of the world.

As colistin had not been widely used, it was

We face a crisis. We are hearing one alarm

still effective. It was also cheap, which encour-

bell after another. Zika and Ebola are two cross-

aged its massive use as a growth promoter in


border epidemics that are currently ongoing.

food production in several countries, including

We are meeting here today to discuss AMR, an-

China.

other cross-border slow moving tsunami. Early

The Chinese findings, which have been rep-

warnings have been issued on AMR and its im-

licated in several other countries, solidify the

pact. We must act.

links between the agricultural use of antibiotics,

We need to agree on the strongest possible

resistance in slaughtered animals, resistance in

action plans. We need to establish an aggres-

food, and resistance in humans. All of the dots

sive model for the rest of the world to follow. We


are connected.

have to make the kind of noise that signals the

If we lose colistin, as several experts are pre-

need for action on a scale appropriate to the

dicting, we lose our last medicine for fighting a

magnitude of this crisis.

number of serious infections.

Let me focus on one of the most recent of

This is a crisis, and it is global. Resistant

these alarm bells relevant to AMR. The detec-

pathogens travel well internationally in people,

tion last year by Chinese scientists of a new

animals, and food. They can also spread di-

resistance mechanism, the mcr-1 gene, sent

rectly from one person to another.


shockwaves through the medical and scientific
communities.

In some countries, as many as 35 percent of
newly detected tuberculosis cases are infect-

The gene is located on a mobile loop of DNA

ed with multi-drug resistant strains right at the

that transfers easily from one bacterial strain

start, indicating direct person-to-person trans-

to others. This is a horizontal transfer of resis-

mission, not faulty treatment.

tance, and it is frightening.
In the Chinese study, the mcr-1 gene conferred resistance to colistin, the last-resort
antibiotic used to treat several life-threatening infections caused by Gram-negative bacteria. Resistance to colistin was detected in
samples from animals and humans and in
food.

We need to take heed of the repeated
warnings.
We need new diagnostics as well as replacement antimicrobials and more vaccines.
We need to find the business models and
incentives to stimulate the relevant R&D.

We need to do more to prevent infections in
the first place.


MARCH 2016 • FO R U M • 7

PPI use associated with increased
CKD risk
ROSHINI CLAIRE ANTHONY

T

he use of proton pump inhibitors (PPIs)
is associated with a higher risk of chronic

kidney disease (CKD) and acute kidney injury (AKI), according to a recent US population
study.
To determine if PPI use was associated with kidney disease in the general population, researchers followed 10,482 participants aged 45-64 in the

creased risk of AKI (HR, 1.64, 95 percent CI,

Atherosclerosis Risk in Communities (ARIC) study

1.22-2.21; p<0.001 and HR, 1.31, 95 percent

for a median of 13.9 years. A separate group com-

CI, 1.22-1.42; p<0.001 for the ARIC and repli-

prising 248,751 patients who were followed up for


cation cohorts, respectively).

a median of 6.2 years formed a replication cohort.

In the replication cohort, a twice-daily dose

In the ARIC study, after adjusting for con-

of PPI was associated with a higher risk than

founders such as demographics, comorbidities

a once-daily dose for both CKD (HR, 1.46, 95

and concomitant use of medications, individu-

percent CI, 1.28-1.67 vs HR, 1.15, 95 percent

als using PPIs at baseline had a higher risk of in-

CI, 1.09-1.21; p<0.001) and AKI (HR, 1.62, 95

cident CKD (hazard ratio [HR], 1.50, 95 percent

percent CI, 1.32-1.98 vs HR, 1.28, 95 percent

CI, 1.14-1.96; p=0.003) compared to nonusers.

CI, 1.18-1.39; p<0.001).


In a time-varying ever-use variable, PPI use was

Previous research has shown that PPIs, indi-

significantly associated with increased CKD risk

cated in the treatment of peptic ulcers, Helico-

(HR, 1.35, 95 percent CI, 1.17-1.55; p<0.001).

bacter pylori infections and gastroesophageal

[JAMA Intern Med 2016;176:238-246]

reflux disease (GERD), are widely used, even

The increased risk was also demonstrated in

in instances where they have not demonstrat-

the replication cohort, where those on PPIs had

ed efficacy. Studies have recommended that

almost 1.2 times the risk of CKD than nonusers

their use in inappropriate situations be cur-

(HR, 1.17, 95 percent CI, 1.12-1.23; p<0.001 af-


tailed. [Postgrad Med J 2007;83:66-68; BMJ

ter adjustment for confounders as well as in a

2008;336:2-3; J Hosp Med 2012;7:421-425]

time-varying ever-use model [HR, 1.22, 95 percent CI, 1.19-1.25; p<0.001]).
PPI use was also associated with an in-

“As a general rule, we should only prescribe
a medication if a patient requires it,” said Dr.
Desmond Wai, consultant hepatologist and


MARCH 2016 • FO R U M • 8

gastroenterologist at Desmond Wai Liver and
Gastrointestinal Diseases Centre, Mount Elizabeth Novena Specialist Centre, Singapore. “Patients with well-controlled GERD or digestive
problems should be taken off medicines once
their problems are solved.”
The authors pointed out that this study was
observational and did not provide evidence
of causality, and called for further research to
identify if PPI use causes kidney damage. They
also did not disregard the possibility that the increased risk of CKD demonstrated in this study
may be unrelated to PPI use.

– all risk factors for kidney disease – it can-


As study participants consumed aspirin,

not be confirmed if PPIs caused kidney dis-

and also had higher incidence of hyperten-

ease, or if those who took PPIs happened

sion, cardiovascular disease, and obesity

to be at risk for kidney disease, Wai said.


MARCH 2016 • N E W S • 9

Chinese diet still too high in salt
and sodium
RADHA CHITALE

S

this was nonsignificant (6.4 g/d, p=0.25). However, all the figures still exceed the WHO-rec-

alt and sodium consumption in China

ommended daily maximums of 5 g/d salt and 2

remains well above the recommended

g/d sodium.


amounts by the World Health Organization
(WHO), according to a new study.

“Although salt added during food preparation
has decreased over time, total sodium intake has

Salt and sodium are major contributors to

not,” the researchers said. “These findings update

high blood pressure and an increased risk of

studies using different methodologies in the 1990s

cardiovascular disease, which the researchers

and 2002 and confirm that simply weighing dietary

note is on the rise in China.

salt intake underestimates sodium consumption in

The researchers used data from two total

China.”

diet studies conducted in 2000 (1,080 house-

Meals eaten out, which typically contain


holds, n=3,725) and between 2009-2011 (1,800

more added salt than those made at home,

households, n=6,072) in 12 provinces repre-

were not recorded as part of either data set as

senting a range of environmental and socioeco-

that would not have been feasible, the research-

nomic strata, though they did not include the far

ers said, which may mean the salt intake of the

west region. [JAMA 2016;315:703-705] 

average person is an underestimate. This may

Foods prepared at home were recorded

apply more to younger people who might eat

and weighed by researchers over 3 days, then

out every day, said co-author Dr. Xiaowei Li of

matching foods were analysed in a lab. The re-


the China National Center for Food Safety Risk

searchers calculated the standardized daily salt

Assessment in Beijing, China, compared to an

and sodium consumption of the “average per-

older person, who might eat out a few times per

son” – a man aged 18-45 years, 63 kg, doing

year.

light activity based on age, weight, sex, and oc-

To combat the rise in noncommunicable dis-

cupation data from the surveys against which to

eases, one of the national targets set by the WHO

compare consumption.

is a 30 percent relative reduction in the mean pop-

Between 2009-2012, the average person’s
salt intake was 9.1 g/d and the average sodium
intake was 5.4 g/d across all the provinces.


ulation intake of salt and sodium.
“The main purpose of the research letter is
to raise the salt issue and hope to draw more

Compared to data from 2000, total salt intake

attention on the possibility to decrease the salt

decreased by 22.2 percent (11.8 g/d, p=0.03)

intakes and try to meet the [WHO’s] reduction

as did sodium intake by 12.3 percent, although

goal,” Li said.


MARCH 2016 • N E W S • 10

Esomeprazole has no advantage
over omeprazole, say researchers
PEARL TOH

S

witching from the generic omeprazole
to the newer, optically pure S-isoform of

omeprazole, sold as esomeprazole, offers little

or no advantage in controlling stomach pH and
treating peptic ulcers, according to a comparative analysis.
“A product is not necessarily better just be-

ysed, no significant difference in the efficacy of

cause it is new or more expensive,” said Pro-

omeprazole and esomeprazole was found when

fessor Fakhreddin Jamali, principal investigator

the drugs were used as part of triple therapy for

and professor of Pharmacy & Pharmaceutical

removal of Helicobacter pylori in both intention-

Sciences at the University of Alberta in Edmon-

to-treat and per-protocol analysis (p=0.63 and

ton, Alberta, Canada.

p=0.57, respectively). Both products were equal-

The monthly cost of treatment for gastric

ly effective at controlling stomach pH in all pH-


acid disorders with esomeprazole is estimated

related outcomes assessed, except for percent-

at US$240 [S$339.3], compared to only US$20

age of patients maintaining a 24 hour gastric pH

[S$28.3] with omeprazole, according to lead

>4, in which esomeprazole was more effective

author Dr. Waheed Asghar, a scientist at the

than omeprazole (p=0.03). Additionally, esome-

University of Alberta.

prazole was marginally superior to omeprazole

Despite previous clinical studies showing esomeprazole is more effective in treat-

(p=0.04) in treating gastroesophageal reflux disease (GERD) symptoms. [Daru 2015;23:50]

ing symptoms of peptic ulcer, the researchers

The study was a comparative analysis of the

noted these were sponsored by the drug mak-


efficacy of omeprazole and esomeprazole in

ers, and revealed in their current study that

randomized controlled trials published in on-

esomeprazole is not therapeutically superior to

line databases. Fourteen studies met the inclu-

omeprazole when used as part of triple therapy

sion criteria. Odds ratio was manually calcu-

to treat ulcers. Jamali urged clinicians to consid-

lated for each outcome of the eligible studies.

er existing evidence for unequivocal therapeutic

“We compared both drugs at equivalent

advantage before prescribing esomeprazole,

doses to avoid unequal comparisons and ex-

particularly since it is far more expensive.

perimental bias that was found in previous re-


Of the 14 randomized controlled trials anal-

views,” said Asghar.


MARCH 2016 • N E W S • 11

A dose of esomeprazole results in greater

ocal evidence exists to suggest patients will

body exposure compared to an equal dose of

benefit from a racemate-enantiomer switch,”

omeprazole, which Asghar said could mask any

Jamali said, as with omeprazole and esome-

pharmacological difference between the two

prazole, for example. “Our data has convinced

drugs. He emphasized the need for indepen-

me to think otherwise... The list of old drugs

dent unbiased clinical trials to assess the true

must be revisited to identify safe and effica-


clinical relevance of the statistical differences

cious medications that are thrown into oblivion

between the two products as reported in the

since their patents have expired.”

media.
“While the idea of using stereochemically
pure drugs is intuitively appealing, no unequiv-

In the case of omeprazole, Asghar recommended that future studies explore the efficacy
and tolerability of higher doses.

Influenza associated with an increased
risk of atrial fibrillation
ROSHINI CLAIRE ANTHONY

I

nfluenza is associated with an increased risk
of atrial fibrillation (AF), a risk that may be re-

duced with vaccination, according to a Taiwanese study.
Individuals who had influenza and did not
receive an influenza vaccination 1 year prior

tion and influenza vaccination 1 year prior was


to enrolment in the study had an 18 percent

comparable to those who were uninfected and

higher risk of AF compared with uninfected,

unvaccinated (OR, 1.136, 95 percent CI, 0.929-

unvaccinated individuals (odds ratio [OR],

1.389; p=0.214).

1.182, 95 percent CI, 1.014-1.378; p=0.032).

The goal of the study was to identify if in-

Conversely, individuals who did not have an

fluenza is a risk factor for AF, and if this risk

infection but had received a vaccination 1 year

could be mitigated by influenza vaccination.

prior had a lower risk of AF (OR, 0.881, 95 per-

Using the Taiwan National Health Insurance Re-

cent CI, 0.836-0.928; p<0.001). [Heart Rhythm


search Database, researchers identified 11,374

2016;doi:10.1016/j.hrthm.2016.01.026]

patients aged ≥20 years who were diagnosed

The risk of AF in those who had an infec-

with AF between 2000 and 2010. Each AF pa-


MARCH 2016 • N E W S • 12

tient was matched with 4 individuals of similar

matory responses and increase of sympathetic

age and gender but without AF (control group,

tone,” said the authors, who acknowledged that

n=45,496).

the precise mechanism behind the influenza-AF

The role of inflammation was suggested by
study authors as a possible mechanism for the

association is still unclear and warrants further

research.

influenza and AF risk association given how

Due to the observational nature of the trial,

prior research has highlighted links between

it cannot be determined if influenza caused the

inflammation and AF pathogenesis as well as

increase in AF risk. However, the authors ad-

influenza and proinflammatory cytokine pro-

vised physicians to consider AF should a pa-

duction. [Eur Heart J 2006;27:136-149; Cyto-

tient with influenza present with palpitations or

kine Growth Factor Rev 2001;12:171-180]

an ischaemic stroke. They also recommended

“Influenza infection might increase the risk
of AF through the activation of systemic inflam-

that high-risk patients receive an annual influenza vaccination.


Wireless capsule as good as catheter
at detecting GERD
JAIRIA DELA CRUZ

E

sophageal pH monitoring through a wireless capsule is as good as catheter-based

monitoring at diagnosing gastroesophageal
reflux disease (GERD), without the discomfort
associated with catheter use, according to a recent evaluation study.
The wireless pH capsule sytem (Bravo) is
a “safe and well-tolerated alternative” to the

sponses during therapy,” they said. [J Neurogastroenterol Motil 2016;22:25-30]

catheter-based pH monitoring, with the ability

In earlier studies in Caucasians and Asians

for prolonged pH recording, said the study au-

with suspected GERD, the diagnostic yield

thors.

of the wireless capsule, which is temporarily

“[It] is recommended in the evaluation of


planted in the patient’s distal oesophageal mu-

patients with refractory GERD, prior to anti-

cosa, was comparable to the catheter. Symp-

reflux surgery, and monitoring of patient re-

tom association with reflux episodes is also


MARCH 2016 • N E W S • 13

similar using both modalities. [Dig Liver Dis

lence of GERD was 6.3 to 18.3 percent after

2008;40:156-160, J Dig Dis 2010; 11:19-27]

2005. In Eastern Asia, cases increased from 5.2

In an Asian study, abnormal reflux was detected with percent of time esophageal pH

in 2005 to 8.5 percent in 2010. [J Neurogastroenterol Motil 2011;17:14-27

<4 of 7.4 percent at 24 hours, 6.3 percent at

One major roadblock to widespread use


48 hours, and 5.8 percent over the 48-hour

of Bravo among GERD patients in Asia is the

study period. Extended recording time with

cost, said Lee. The system is 75 percent more

Bravo led to an incremental diagnostic yield

expensive than nasal catheters (US$225 ver-

of 30 percent. The pH results could, in the

sus US$62, respectively).

meantime, serve as a reference values in the

“However, in an ideal situation where cost is

diagnosis of GERD, said principal author Dr.

not an issue, we would recommend Bravo cap-

Yeong Yeh Lee from the Universiti Sains Ma-

sule for better tolerability, and for its ability to

laysia in Kelantan, Malaysia. However, the 24-


evaluate the efficacy on-PPI,” Lee said. “If cost

hour pH value of <7.4 percent is still too high

is an issue, then pH probe is recommended for

and a percentage time pH <4 of 5.8 over 48

exclusion of GERD off-PPI.”

hours might be more appropriate for Asian
patients. [J Dig Dis 2010;11:19-27]
In Southeast and Western Asia, the preva-

For non-acidic reflux detection, the pH-impedance probe is superior over both pH alone
and Bravo capsule, he added. 

Eye abnormalities in microcephalic
infants associated with Zika virus
ELVIRA MANZANO

V

ision-threatening eye abnormalities in infants with microcephaly may be associated

with congenital intrauterine infection due to Zika
virus, a new study in Brazil has shown.
“A high proportion of the infants with microcephaly had ophthalmologic lesions,” said lead
study author Dr. Bruno de Paula Freitas from the


transmission settings, ophthalmologists should

Department of Ophthalmology, Hospital Geral

be aware of the risk of congenital Zika virus-as-

Roberto Santos in Salvador, Brazil. “In high-

sociated ophthalmologic sequelae.”


MARCH 2016 • N E W S • 14

De Paula Freitas and colleagues from

sity Feinberg School of Medicine, Chicago, Illi-

the Federal University of São Paulo in Bra-

nois, US said the study implicates infection due

zil analysed data of 29 infants with micro-

to Zika virus as “the cause of chorioretinal scar-

cephaly (head circumference ≤32 cm) diag-

ring” and possibly other ocular abnormalities in

nosed with congenital Zika virus in December


infants with microcephaly born in Brazil.

2015 and found that most infants had bilat-

Six months after the Zika virus outbreak in Bra-

eral macular and perimacular lesions as well

zil, the number of newborns with microcephaly

as optic nerve abnormalities. [JAMA Ophthalmol

has increased to 3,174 in January this year. Cur-

2016;doi:10.1001/jamaophthalmol.2016.0267]

rently, there is a 20-fold reported increase of mi-

Of 29 mothers, 23 reported suspected signs
and symptoms of Zika virus (arthralgia, head-

crocephaly cases in parts of Brazil that are temporally associated with the Zika virus.

ache, fever, itch and rash) during pregnancy.

“However, this association is still presump-

Eighteen of them experienced symptoms dur-


tive because definitive serologic testing for Zika

ing the first trimester of pregnancy.

virus was not available in Brazil at the time of

Abnormalities of the eye were observed in 10

the outbreak and confusion may occur with

infants with microcephaly. Of the 20 eyes in 10

other causes of microcephaly which can can

children, 17 eyes had ophthalmoscopic abnor-

be genetic, metabolic, drug related, or due

malities. Bilateral abnormalities were found in

to perinatal insults such as hypoxia, malnutri-

seven of 10 infants with ocular lesions, the most

tion, or infection,” said Jampol and Goldstein.

common of which were focal pigment mottling

“Similarly, the currently described eye lesions


of the retina and chorioretinal atrophy in 11 of

are presumptively associated with the virus.”

the 17 eyes with abnormalities. Optical nerve

[JAMA Ophthalmol 2016;doi:10.1001/jamaoph-

abnormalities were also observed in eight eyes.

thalmol.2016.0284]

“Our findings can help guide clinical man-

However, given the findings, clinicians in

agement and practice... infants with microceph-

areas where Zika virus is present should per-

aly should undergo routine ophthalmologic

form ophthalmologic examinations on all mi-

evaluations to identify such lesions,” said the

crocephalic babies, said the commentators. To

authors.


suggest ophthalmic screening for all babies

In a related commentary, Drs. Lee M. Jampol
and Debra A. Goldstein of Northwestern Univer-

born in Zika epidemic areas is nonetheless
“premature.”


MARCH 2016 • N E W S • 15

Early menarche may increase risk of
gestational diabetes
ROSHINI CLAIRE ANTHONY

E

arlier age of menarche is significantly
linked to a higher risk of gestational dia-

betes mellitus (GDM) independent of other risk
factors, according to a recent study.
Women whose age at menarche was ≤11

years had a 39 percent increased risk of GDM
compared to those whose age at menarche was

from 27,482 women in the Nurses’ Health Study

≥14 years (relative risk [RR], 1.39, 95 percent CI,


II, researchers used a baseline questionnaire at

1.19-1.63; p<0.0001) after adjusting for age, race

study onset in 1989 to identify age at menarche.

and family history of diabetes. The risk of GDM

The women were followed-up until 2001. There

reduced with increasing age at menarche (RR,

were 1,404 cases of GDM, 346 of which were re-

1.13, 95 percent CI, 0.97-1.32 and RR, 1.10, 95

current cases.

percent CI, 0.95-1.29; p<0.0001 for menarche at
age 12 and 13 years, respectively).

Previous research investigating the link between early menarche and diabetes has pro-

Prepregnancy body mass index (BMI) was

duced mixed results. One study demonstrated a

found to mediate this link in a segment of the


link between early menarche and increased risk

study population (estimated increased risk of 42.1

of type 2 diabetes which appeared to be medi-

percent, 95 percent CI, 17.9-66.3; p=0.0007). [Di-

ated by increased BMI, while another found no

abetes Care 2016;doi:10.2337/dc15-2011/-/DC1]

link between age at menarche and risk of GDM.

After adjusting for other factors including

[Diabetologia 2008;51:781-786; Diabetes Res

childhood adiposity and lifestyle in adulthood

Clin Pract 2011;93:437-442]

(eg, physical activity, smoking, and oral con-

“The precise mechanism by which early age

traceptive use), the association between early

at menarche may increase the risk of GDM is


menarche and GDM remained significant (RR,

not clear,” said researchers.

1.34, 95 percent CI, 1.14-1.58, RR, 1.13, 95 per-

“It is plausible that age at menarche may be

cent CI, 0.97-1.31 and RR, 1.11, 95 percent CI,

related to GDM risk through its association with

0.95-1.29; p=0.0005 for menarche at ≤11, 12

hormonal changes.” Thus, further studies to

and 13 years, respectively).

determine the exact mechanisms are required,

Based on a cohort of 42,109 pregnancies

they concluded.


MARCH 2016 • N E W S • 16

High-fibre diet associated with
improved lung health
ROSHINI CLAIRE ANTHONY


A

diet high in fibre may help improve lung
health, according to new research from

the US.
Individuals with the highest fibre intake
(>17.5 g/day) had mean FEV1 and FVC levels that were 82 and 129 ml higher than those
with the lowest fibre intake (<10.75 g/day)
(p=0.05 and p=0.01, respectively). Individu-

ciations between dietary fibre and lung func-

als with a mid-range fibre intake (13.46-≤17.5

tion. One study showed that higher dietary fi-

g/day) also had higher FEV1 and FVC levels

bre intake was associated with reduced COPD

(82 and 115 ml higher) than those with the

prevalence and better lung function, while an-

lowest fibre intake (p=0.04 and 0.003, respec-

other demonstrated an association between


tively). [Ann Am Thorac Soc 2016;doi:10.1513/

higher fibre intake and lower cardiovascular,

AnnalsATS.201509-609OC] Those with the high-

infectious and respiratory-related deaths. [Am

est intake of fibre also had better lung function

J Epidemiol 2008;167:570-578; Arch Intern

(determined by airflow patterns) and less airflow

Med 2011;171:1061-1068]

restriction compared to those with the lowest in-

Among theories suggested to explain the

take (68.3 vs 50.1 percent; p=0.001 and 14.8 vs

association include higher fibre intake being

29.8 percent; p=0.001, respectively).

associated with lower systemic inflammation

Smoking and body mass index (BMI) did


and C-reactive protein (CRP) levels, as well

not appear to modify the association between

as fibre-induced alterations to gut microbiota.

fibre intake and lung function.

According to study author Associate Pro-

Study subjects were 1,921 individuals aged

fessor Corrine Hanson from the University of

40-79 from the National Health and Nutrition

Nebraska Medical Center, Nebraska, US, indi-

Examination Surveys (NHANES) from 2009 to

viduals who would most benefit from a fibre-

2010. Data on fibre intake, lung function mea-

focused diet are those with restrictive lung

surements, airflow restriction, and obstruction

disease.


based on GOLD and Spirometry Grade (SG)
classifications were collected and analyzed.
Previous studies have demonstrated asso-

“This group [restrictive lung disease] is very
heterogeneous, and studies such as COPDGene have identified a sub-group defined as


MARCH 2016 • N E W S • 17

“metabolic”. Many people in this group tend to

provide insight into the mechanism behind

have other metabolic complications including

the dietary fibre-lung function association.

systemic inflammation and obesity. Fibre may

“Because lung function declines slowly, long-

have a beneficial impact on those metabolic

term studies following both dietary intake and

complications as well.”

lung function would be helpful. Including both


Hanson recommended follow-up studies

of these measures in large cohort studies would

to measure the impact of fibre on systemic

provide further epidemiological evidence,” she

and pulmonary markers of inflammation and

said.



MARCH 2016 • N E W S • 18

Eluxadoline offers symptom relief
from IBS with diarrhoea
PEARL TOH

T

reatment with eluxadoline, a new oral medication, relieved two major symptoms of ir-

ritable bowel syndrome with diarrhoea (IBS-D)
— abdominal pain and diarrhoea, according to
a study based on two phase III randomized controlled trials. [N Engl J Med 2016;374:242-253] 
Currently available treatment options for IBSD are limited, particularly options that relieve
both abdominal pain and diarrhoea. Study coauthor Professor Marc Zuckerman, chief of the
Division of Gastroenterology at Texas Tech University Health Sciences Center in El Paso, Texas, US, said eluxadoline provides a new option

for treating IBS-D patients that do not respond
to standard management with lifestyle changes
and over-the-counter medication.

The researchers found that by week 12,

“This is a new first-in-class drug, with a unique

abdominal pain and diarrhoea improved in 24

mechanism of action in that it is a mu opioid re-

(study 1, p=0.01) and 29 (study 2, p<0.001)

ceptor (OR) agonist, a kappa OR agonist, and a

percent of patients given the 75 mg dose of

delta OR antagonist, targeting receptors in the

eluxadoline, and 25 (study 1, p=0.004) and

gastrointestinal (GI) tract,” said Zuckerman.

30 (study 2, p<0.001) percent of patients tak-

Co-author Dr. Brian Lacy, professor of medi-

ing 100 mg dose; compared with the placebo


cine and chief of the Section of Gastroenterol-

group which saw an improvement in 17 (study

ogy and Hepatology at Dartmouth-Hitchcock

1) and 16 (study 2) percent of the patients. Sim-

Medical Center in Lebanon, New Hampshire,

ilar efficacy results were sustained over the 6

US, said due to eluxadoline’s mixed action on

month treatment period of the studies (study 1:

different subtypes of OR and its very limited ab-

p=0.11 for 75 mg, p<0.001 for 100 mg; study 2:

sorption from the GI tract, it should not cause

p=0.001 for 75 mg, p<0.001 for 100 mg). The

any problems typical of opioids, such as som-

study is sponsored by Furiex Pharmaceuticals,

nolence or addiction.


an affiliate of Allergan.


MARCH 2016 • N E W S • 19

Common adverse events associated with eluxadoline treatment were constipation, nausea, and

colic, I also caution them that they may be at
increased risk,” Lacy agreed.

abdominal pain; while the most serious adverse

Lacy said that while no medication has

event documented was pancreatitis, affecting 0.3

been shown to improve IBS-D symptoms in

percent of the 1,666 patients enrolled in the safety

all groups of patients, eluxadoline was effec-

population. However, the authors noted that the

tive for both men and women as well as young

discontinuation rate due to adverse reactions was

and old patients, in relieving abdominal pain


low.

and diarrhoea. He said the drug also worked

Nonetheless, erring on the side of caution,

well for IBS-D patients who have previously

Zuckerman advised clinicians to keep in mind

received but failed the diarrhoea medication

three conditions before prescribing eluxadoline:

loperamide.

sphincter of Oddi dysfunction, pancreatitis, and

Thus far, there are no direct comparisons

alcohol abuse. Additionally, he said eluxadoline

with similar prescription drugs for this condi-

should be avoided in patients with chronic con-

tion, such as rifaximin or alosetron. Lacy said it

stipation.


would be interesting to do a direct comparison

“If [the patients] have a history of gallbladder
problems (known stones or sludge) or biliary

study of eluxadoline and alosetron and/or even
rifaximin in the future.
 

Ethnicity could determine flu vaccine
response
RADHA CHITALE

P

eople may respond differently to flu vaccines based on their ethnicity, according

to researchers who examined a population of
Asians, Europeans, and Africans.
The results could help fine tune individual
and population responses to flu vaccines.
“This will change our understanding of how
to achieve universal vaccine responsiveness in
a population,” said lead researcher Dr. Wayne

at the Dana-Farber Cancer Insitute in Boston,

Marasco, a cancer immunologist and virologist

Massachusetts, US.



MARCH 2016 • N E W S • 20

The researchers used blood samples from
volunteers who received the H5N1 influenza

commonly among, broadly, Asians (n=504),
Europeans (n=503), and Africans (n=661).

vaccine in 2007 to examine variations in the

The researchers proposed creating a com-

IGHV1-69 gene, which makes antibodies that

plete haplotype map of all 50 IGHV genes, in-

bind to the “stem” portion of the common influ-

cluding IGHV1-69, in order to catalogue all the

enza A virus – the stem being less variable com-

potential genetic variations. The map should

pared to the “head” region of the virus where

be larger and include a complement of differ-


other flu antibodies tend to bind and therefore

ent ethnicities as well.

a more promising target for a long-lasting vaccine. [Sci Rep 2016;6:20842]

“This advance will naturally lead to the development of complementary high-through-

Each person has the gene in two of 14 forms

put genotyping tools that may prove useful for

which vary in effective flu virus response – some

predicting vaccine responsiveness at the indi-

do not respond at all. The researchers con-

vidual and population levels,” the researchers

firmed this in tests as well as finding that im-

said.

mune response varied in relation to the number
of gene copies a person had.

“Taken together, these analyses indicate that
interrelationships... likely exhibit population-


In a first finding of its kind, the researchers

specific patterns that may have broad implica-

also showed that gene variants varied across

tions for mounting broadly protective HV1-69-

ethnicity with certain variants found much more

sBnAbs [antibody] responses.”


MARCH 2016 • N E W S • 21

Cheaper, nonsurgical procedure
could help obese patients lose weight
RADHA CHITALE

A

less invasive stomach-shrinking procedure
that is cheaper than normal bariatric sur-

gery reduced body weight by more than half
in obese patients who received it, according to
a small study at the Mayo Clinic in Rochester,
Minnesota, US.
The procedure, called endoscopic sleeve
procedure.


Pa-

tools to go into the stomach via the mouth and

tients

reported

oesophagus and suture it into a tube-like shape.

good

outcomes

Twenty-five obese patients (mean BMI 35.5

and fast recovery

kg/m ; mean age 47.6 years) who got the pro-

following the pro-

cedure saw a 54 percent reduction in their body

cedure and were

weight over a median 9-month follow-up period.

back to their nor-


[Clin Gastroenterol Hepatol 2015; doi:10.1016/j.

mal activities with-

cgh.2015.12.030]

in 3 days. It also

2

Endoscopic analysis at 3 months post-pro-

costs about two-

cedure showed intact sutures. Slower gastric

thirds less than

emptying meant patients reported earlier full-

bariatric surgery,

ness during mealtimes and had significant,

the

long-lasting weight loss. There was also a trend

reported. 


towards greater insulin sensitivity.

Photo courtesy of Barham K. Abu Dayyeh, MD, MPH, Mayo Clinic, Rochester, Minnesota, US.

gastroplasty, uses “off the shelf” endoscopy

researchers

The procedure

Endoscopic sleeve gastroplasty
uses a full thickness endoscopic
suturing device to shrink the
stomach into a smaller, tube-like
shape.

Three serious adverse events (a perigastric

may be helpful

inflammatory collection, a pulmonary embo-

for obese patients

lism, and a small pneumothorax) were resolved

who cannot have bariatric surgery – which in-

without surgery.


cludes Roux-en-y gastric bypass, laparoscopic

Endoscopic sleeve gastroplasty requires no

adjustable gastric banding, sleeve gastrectomy,

incisions compared with other types of bariatric

and duodenal switch with biliopancreatic diver-

surgery, though it is done under anaesthesia,

sion – due to access, cost, or associated risks.

takes under 2 hours, and can be an outpatient

The researchers note only 1 to 2 percent of eli-


MARCH 2016 • N E W S • 22

gible patients go ahead with bariatric surgery.

offers an effective weight loss intervention at

“Given the low use of bariatric surgery and

lower cost and higher patient satisfaction, po-


limited effectiveness of lifestyle changes and

tentially filling this gap in the management of

drug treatments, a significant gap exists in our

obesity.”

current approach to obesity,” said lead author

The procedure is not indicated for patients

Dr. Barham K. Abu Dayyeh from the Department

with gastrointestinal bleeding, hiatial hernia

of Gastroenterology and Hepatology at the

larger than 3 cm, or those who have had stom-

Mayo Clinic. “Endoscopic sleeve gastroplasty

ach surgery.

Delirium common in older patients
after gastrointestinal surgery
ELVIRA MANZANO

P


ostoperative delirium (POD) may be a common occurrence in older patients following

gastrointestinal (GI) surgery, according to a systematic review and meta-analysis, highlighting
the need for physicians to identify those at risk
for POD and to come up with tailored interventions.
“Delirium is not exclusive to medical health-

ies. Patients’ age ranged from 68 to 81 years

care settings,” said lead investigator Dr. Anna

and most underwent elective colorectal surgery.

Scholz from the Cardiff University in Cardiff,

POD incidence ranged from 8.2 to 54.4 per-

Wales, UK. POD was tied to longer hospital stay

cent in these patients following GI surgery. After

(mean difference [MD], 4.56 days) and higher

assessing all risk factors, advanced age, poor

risk of dying in older patients (odds ratio [OR],

physical status (ASA grade ≥3), low body mass

4.03) compared to patients without delirium. [Br


index, low serum albumin levels, intraoperative

J Surg 2016;103:e21-28]

hypotension, perioperative blood transfusion,

Using five databases, Scholz and her team

and history of alcohol excess appeared to dem-

searched the available evidence in general sur-

onstrate significantly higher risks for POD in a

gery and analysed data on 1,427 patients (318

pooled analysis.

with delirium and 1,109 without) from 11 stud-

“The risk factors identified in this review will


MARCH 2016 • N E W S • 23

aid the planning of future studies to explore the

Delirium is common but often undiagnosed


extent of their effect, as well as the impact of tai-

in geriatric post operative patients and can

lored interventions,” Scholz and team said. “By

result in falls, aspiration pneumonia, and pull-

stratifying patients, intervention studies can be

ing of tubes or lines in some patients. Thus,

planned, which should result in improvements

recognition and treatment of POB is critically

in patient care.”

important.

Bisphosphonates don’t increase
gastric and oesophageal cancer risk
KAVITHA G. SHEKAR

B

isphosphonates do not increase the risk of
gastric or oesophageal cancer, said Lon-

don-based researchers in a systematic review

and meta-analysis they hope might ease rising
speculation on bisphosphonates’ possible cancer links.
“Bisphosphonates in general and [the commonly prescribed bisphosphonate] alendro-

ported bisphosphonate prescription in gastric

nate in particular are being recommended by

and oesophageal cancer from inception until

current osteoporosis prevention guidelines to

March 2015. Trials were based in the US, UK,

increasing numbers of men and women in pre-

Denmark, and Taiwan, and non-case-control

dominantly older age groups,” said author Dr.

or cohort studies, and those that did not report

Ellen Wright from the Department of Primary

odds ratio (OR), hazard ratio (HR), relative risk

Care and Public Health Sciences, King’s Col-

or 95 percent confidence interval (CI), were


lege London, London, UK.

excluded. [BMJ Open 2015;doi:10.1136/bmjo-

These drugs are known to cause dyspepsia,

pen-2014-007133]

inflammatory changes, and mucosal abnormali-

The number of bisphosphonate patients

ties; however, their ability to cause malignancy

in the cohort studies ranged from 30,606 to

remains unknown, Wright said.

55,090, and patient numbers in the case-con-

The analysis included 11 studies (5 cohort
studies and 6 case-control studies) that re-

trolled studies were 116 to 5,364.
Compared with nonusers, the researchers