NEWS & INSIGHTS AUGUST 2016

Empagliflozin delays
kidney disease and dialysis
in diabetes outcome trial

NEWS CONFERENCE
Glucocorticoid use COVERAGE
tied to elevated risk Late-onset asthma
of S. aureus infection common but often
underdiagnosed
in the elderly

IN PRACTICE CONFERENCE
Managing osteoporotic COVERAGE
spinal fractures Eye benefits of tight
in primary care glycaemic control
persist over time

Empagliflozin delays kidney disease
and dialysis in diabetes outcome trial
CHRISTINA LAU
E mpagliflozin significantly delays the pro-
gression of kidney disease and reduces
renal events in patients with type 2 diabetes
mellitus (T2DM) at high cardiovascular (CV)
risk, new data from the EMPA-REG OUTCOME
(Empagliflozin-Renal Excretion of Glucose Out-
come) trial have shown.
A 39 percent reduction in risk of incident
or worsening nephropathy was demonstrated
with empagliflozin vs placebo (p<0.001) in a
trial population with one-third of patients having
prevalent kidney disease (estimated glomeru-
lar filtration rate [eGFR], 30-60 mL/min/1.73m2
and/or macroalbuminuria) at baseline. [N Engl J
Med 2016; doi:10.1056/NEJMoa1515920]
Both the 10 mg and 25 mg doses of em-
pagliflozin demonstrated the same effect on
nephropathy, reported lead author Professor
Christoph Wanner of the Wurzburg University
Clinic, Wurzburg, Germany, at the American
Diabetes Associations 76th Scientific Sessions
in New Orleans Louisiana, US. The effect was
consistent in different subgroups of patients.
While empagliflozins effect on nephropathy
was driven by a 38 percent risk reduction in
new-onset macroalbuminuria (p<0.0001), the
results also showed a 55 percent reduced risk
of initiation of dialysis (p=0.049) and a 44 per-
cent reduced risk of doubling of serum creati-
nine (p=0.0009) with empagliflozin vs placebo.
AUGUST 2016 2
When the hard renal outcomes of dou-
bling of serum creatinine, initiation of dialysis
and death due to renal disease were analysed
together, a 46 percent risk reduction was seen
with empagliflozin vs placebo (p<0.001), with
the curves beginning to diverge at 1.5 years,
said Wanner.
The researchers also analysed renal out-
comes in patients with prevalent kidney disease
at baseline. In these patients, empagliflozin
reduced the risk of incident or worsening ne-
phropathy by 42 percent (p<0.001).
eGFR remained stable in the empagliflozin
arms throughout the study, but a natural pro-
gression was seen in the placebo arm, said
Wanner.
The adjusted mean difference in eGFR
change from baseline with empagliflozin vs pla-
cebo was 4.7 mL/min/1.73m2 when patients were
followed up at a median duration of 34 days after
their last on-treatment eGFR measurement, he
continued. As nephrologists, we all know what
4.7 mL/min/1.73m2 means in pushing dialysis

further down the road.
The safety and tolerability of empagli-
flozin in patients with chronic kidney disease
at baseline were similar to that in the overall
trial population, added Wanner. Acute renal
failure and acute kidney injury occurred at low-
er rates in the empagliflozin vs placebo arm.
The EMPA-REG OUTCOME trial was conduct-
ed in 7,020 T2DM patients with established CV
disease. Patients were randomized to receive
Stenting through the wrist reduces
risk of death in heart disease patients
PEARL TOH
I nserting stents by radial access for per-
cutaneous coronary intervention
reduced bleeding and risk of death in pa-
(PCI)
tients with coronary artery disease (CAD)
as opposed to femoral access, according
to a recent meta-analysis of 24 randomized
trials.
These findings support the use of radial ac-
cess as the default approach for coronary an-
giography followed by PCI in the whole spec-
trum of patients with CAD undergoing invasive
management, and strongly support a change
in the femoral first paradigm to a radial first
approach, said lead author Dr. Giuseppe Fer-
rante of the Department of Cardiovascular
Medicine at Humanitas Research Hospital in
Milan, Italy.
AUGUST 2016 3
empagliflozin 10 mg or 25 mg daily or place-
bo, and assessed for the primary outcome of
major adverse CV events (CV mortality, non-
fatal MI, nonfatal stroke). Assessment of renal
outcomes was a pre-specified objective, with
incident or worsening nephropathy defined as
progression to macroalbuminuria, doubling of
serum creatinine accompanied by eGFR 45
mL/min/1.73m2, initiation of dialysis, or death
due to renal disease.
In the meta-analysis which pooled data
from 22,843 patients in 24 randomized stud-
ies, patients who underwent radial access
had a 29 percent lower risk of death from any
cause compared with those who had inter-
vention through femoral access (odds ratio
[OR], 0.71, 95 percent confidence interval [CI],
0.59-0.87; p=0.001). [JACC Cardiovasc Interv
2016;doi:10.1016/j.jcin.2016.04.014]
Risk of major adverse cardiovascular events

(MACE) also decreased by 16 percent with radi-
al access in comparison to femoral access (OR,
0.84, 95 percent CI, 0.75-0.94; p=0.002).
Additionally, there was a significant reduc-
tion of risks for major bleeding by 47 percent
(OR, 0.53, 95 percent CI, 0.42-0.65; p<0.001)
and major vascular complications by 77 percent
(OR, 0.23, 95 percent CI, 0.16-0.35; p<0.001)
with radial access in contrast to femoral access.
Risks of stroke and myocardial infarction
were similar using both methods.
Importantly, the researchers found that radial
access improved clinical outcomes mentioned
above across a broad spectrum of stable and
unstable CAD, including ST segment elevation
myocardial infarction (STEMI), non-ST segment
elevation (NSTE) acute coronary syndromes
(ACS), and unstable angina.
As much as possible, all eligible patients
with a good radial pulse and positive Allens
test [could be considered for transradial PCI],
said Dr. Jack Tan Wei Chieh, a senior consultant
cardiologist and director of the Coronary Care
Unit at the National Heart Centre Singapore in
Singapore who was unaffiliated with the study.
At least 70 percent of all his pre-scheduled
cases for coronary intervention in Singapore were
performed through radial access, he added.
Several anatomic features give the wrist
an advantage over the groin, said Dr. John
Bittl, a cardiologist at Munroe Regional Medi-
cal Center in Ocala, Florida, US, in a separate
commentary. With the redundant vascular
supply of the hand loss of a radial pulse has
fewer consequences than loss of the common
femoral artery pulse. [JACC Cardiovasc Interv
AUGUST 2016 4
2016;doi:10.1016/j.jcin.2016.05.026]
However, patients with small radial arteries,
upper-extremity haemodialysis access, and ab-
normal Allens test results are not favourable
candidates for PCI through radial access, he
said.
Tan agreed, adding that, [Transradial PCI
is] not for renal failure patients and post-by-
pass cases. Patients who require larger French
guide catheters, or who have poor radial puls-
es with failure to demonstrate good collateral
filling of the hand from the ulnar artery [are
also not recommended].
Certain anatomical features of Asians could
also limit radial access for the procedure, said
Tan.
The radial accesses for elderly ladies
are smaller, more tortuous and tend to have
spasms with minimal manipulation.
The main challenge in performing transradial
PCI lies in overcoming the learning curve to at-
tain mastery of technical skills, said Tan. Previ-
ous studies have reported that high procedure
volumes were often required by cardiologists to
achieve proficiency. [Int J Cardiol 1998;64:231
239]

A comprehensive and fair solution
to the price of medicines
A fter a long dry spell, the pharmaceutical
research industry has brought to mar-
ket a spate of innovative treatments that can
extend life and often have fewer side effects
than older treatments. But these medicines
are not affordable to most of the people who
need them. Recent treatments for hepatitis C
and cancer both widespread conditions
globally can cost from US$50,000 annually
to well over US$150,000.
At the other end of the spectrum, the gener-
ic pharmaceutical industry is losing interest in
manufacturing older, off-patent medicines be-
cause the market price has been slashed to a
level that it no longer provides an incentive to
produce them. The result is either low-quality
medicines, or no medicines at all. Two clear
examples of this phenomenon are Benzathine
penicillin, the antibiotic of choice for certain bac-
terial infections, and methotrexate, used to treat
arthritis, psoriasis, and certain cancers. These
products, still needed and often prescribed, are
frequently unavailable in health systems.
These recent trends represent a two-fold set-
back: on the one hand, new medicines are out
of reach of even the wealthiest countries, on the
other, older medicines are in great shortage.
Different prices in different countries
A study published in PLOS Medicine at
the end of May shows that the prices of two
new medicines for treating hepatitis C vary
AUGUST 2016 FO R U M 5
greatly between
countries world-
wide, raising se-
rious concerns
about the viabil-
ity of reducing
the global hepa-
titis C burden.
After adjusting
WHO Photo
for average 2015
exchange rates
Marie-Paule Kieny
and purchasing WHO Assistant Director-General
power, the study Health Systems and Innovation
reveals that the cost of treating the entire hep-
atitis C infected population in each of the 30
countries examined would range from 10.5
percent of total pharmaceutical expenditure in
the Netherlands to 190.5 percent in Poland.
Some governments have found national
solutions to high prices, like Australia, where
the Pharmaceutical Benefits Scheme is the
single negotiator and purchaser of drugs for
the country and makes medicines available at
fixed prices.
Others are seeking solutions for specific
medicines, like Colombias recent plan to al-
low a generic copy of the cancer drug imatinib.
The current price of the branded medicine for
1 year of treatment per patient is more than
double the nations per-capita income.
Others still have put in place mechanisms
to address drug shortages. In the US, which

has been experiencing increasing drug stock-
outs, the Food and Drug Regulatory Authority
has established a fast-track review process
for medicines in short supply to incentivize
companies to keep producing them.
But from the point of view of global public
health, the way forward must be comprehen-
sive and sustainable if we are to eradicate treat-
able infectious illnesses, effectively address the
upsurge of noncommunicable and chronic dis-
eases and care for our ageing populations.
Unknown pricing mechanisms
Amid public outcry, political battles and
media articles, no one seems to under-
stand how, exactly, medicine prices are
set. For years, pharmaceutical research
companies have cited the large invest-
ment of time and resources that go into
bringing a drug to market. More recently,
they argue that their medicines are actu-
ally saving money by preventing expen-
sive medical interventions like surgery and
hospitalization.
But whatever the argument used, the price
setting mechanisms for commodities that are
inextricably linked to peoples health and sur-
vival must be made more transparent so that
we can, as a global community, devise effec-
tive solutions.
AUGUST 2016 FO R U M 6
To that end, WHO is planning to convene
governments, patient groups and industry
stakeholders to develop a fair pricing mod-
el that can affordably deliver the medicines
needed by patients while keeping companies
interested in developing new and better treat-
ments and producing generic treatments. That
model will need to hinge on greater transpar-
ency in industrys research and development
and marketing approaches; it will also need to
understand what the inputs are into price set-
ting, as well as the barriers companies face in
bringing new products to market.
In late 2015, we entered the era of sus-
tainable development, with universal health
coverage at the centre of global health ef-
forts. That means that by 2030, the deadline
for the Sustainable Development Goals, all
countries must be able to provide full cov-
erage for quality health services to their en-
tire populations. The only way we can reach
that objective is to enter a social contract
between the public and private spheres so
that innovation and generic production can
respond effectively to global public health
needs both in the quality and effective-
ness of the treatments, their availability, and
their affordability.
This commentary was first published on the WHO public website.

Less antibiotic prescription
does not increase risks of RTIs,
except pneumonia, quinsy
PEARL TOH
R educed antibiotic prescription for respi-
ratory tract infections (RTIs) in primary
care settings was associated with a slight
increase in the risks of pneumonia and peri-
tonsillar abscess (quinsy), but not other RTIs,
implying a need to review current antibiot-
ic prescribing practice in view of increased
drug resistance in bacteria, a new study
suggested.
Many RTIs are largely self-limiting, but an-
tibiotics continue to be prescribed for about
50 percent of consultations for RTIs in primary
care, said the researchers, noting that wide-
spread unnecessary use of antibiotics have led
to increased antimicrobial drug resistance.
The study analysed the incidence of RTIs from
610 general practices in the UK using 411,226
patient records over 10 years (2005-2014),
equivalent to 45.5 million person-years of patient
follow-up. [BMJ 2016;doi:10.1136/bmj.i3410]
In general, the proportion of RTI consul-
tations requiring antibiotic prescriptions de-
creased for both men and women over the 10
years (from 53.9 to 50.5 percent for men, and
from 54.5 to 51.5 percent for women).
New incidence of meningitis, middle ear
infections (mastoiditis), and peritonsillar ab-
scess saw a yearly decrease of 5.3, 4.6, and
AUGUST 2016 N E W S 7
1.0 percent, respectively during the period,
while pneumonia incidence increased by 0.4
percent yearly.
A 10-percent reduction in antibiotic prescrip-
tion increased the relative risk for pneumonia
by 12.8 percent and 9.9 percent for peritonsil-
lar abscess (p<0.001 for all), after adjusting for
age and sex.
Put differently, if 10 percent fewer antibiot-
ics were prescribed for RTIs in a general prac-
tice (GP) with an average size of 7,000 patients
listed over 10 years, equivalent to 2,030 fewer
antibiotic prescriptions, one additional case of
pneumonia could be expected each year and
an additional case of peritonsillar abscess could
be expected each decade.
However, no increase in the risk of intracra-
nial abscess, meningitis, mastoiditis, empyema,
and Lemierre syndrome was observed with re-
duced antibiotic prescriptions.

Even a substantial reduction in antibiotic
prescribing may be associated with only a small
increase in the numbers of [pneumonia and
peritonsillar abscess] cases observed, said
lead author Professor Martin Gulliford of the
Department of Primary Care and Public Health
Sciences at Kings College London in London,
UK, noting that both the complications can be
readily treated when identified.
Our results suggest that, if antibiotics are
not taken, this should carry no increased risk of
more serious complications, he added.
Nonetheless, current guidelines for manag-
ing RTIs recommend that specific patient sub-
groups who have a higher risk of pneumonia,
such as those with comorbidities or clinical
presentation of serious complications, the very
young, or the very old should be considered for
immediate antibiotic prescription. [Med Decis
Making 1981;1:239-246]
Antibiotic treatment of RTIs, in which most of
Early ART averts HIV-1 transmission
to sexual partners
STEPHEN PADILLA
E arly treatment of human immunodeficiency
virus type 1 (HIV-1) with antiretroviral thera-
py (ART) prevented transmission of the disease
in sexual partners, according to the HIV Preven-
tion Trials Network (HPTN) 052 study.
Previous observational studies involving se-
AUGUST 2016 N E W S 8
the cases are caused by viruses and are often
self-limiting, offers negligible benefit to patients,
said the authors, suggesting that reduced anti-
biotic prescriptions for RTIs could minimize side
effects such as vomiting, rashes, and diarrhoea.
Still, general practitioners might feel obliged
to prescribe antibiotics for RTIs due to patients
expectations and concerns about the safety of
not prescribing antibiotics that could lead to
missed opportunities for treatment. [Scand J
Prim Health Care 2015;33:11-20]
A delayed antibiotic prescribing strategy,
whereby a prescription is issued but not used
until symptoms were deemed to have failed to
improve, might help reduce antibiotic use in
managing RTIs. [Cochrane Database Syst Rev
2013;4:CD004417]
This would be expected to reduce the risks
of antibiotic resistance, the side effects of an-
tibiotics, and the medicalization of largely self-
limiting illnesses, said the researchers.

rodiscordant couples have shown that ART in
persons with HIV-1 infection lowers the risk of
sexual transmission of the virus. The HPTN 052
trial was designed to determine the effect of
ART on the transmission of HIV-1 from infected
person to their sexual partners, according to
researchers.
A total of 1,763 index participants were ran-
domized to receive either early (n=886) or de-
layed (n=877) ART. In the early-ART group, par-
ticipants started therapy at enrolment (CD4+
count, 350 to 550 cells/mm3). In the delayed-
ART group, participants began therapy after 2
consecutive CD4+ counts fell below 250 cells/
mm3 or if an illness indicative of the acquired im-
munodeficiency syndrome (ie, an AIDS-defining
illness) developed.
In the interim analysis of data, investigators
found that early ART was associated with a 96
percent lower risk of index-to-partner, geneti-
cally linked HIV-1 infections than was delayed
ART. The trial continued to assess the durability
of the effect of ART for the prevention of HIV-1
transmission.
The primary endpoint of the study was the
diagnosis of genetically linked HIV-1 transmis-
sion in the previously HIV-1negative partner in
AUGUST 2016 N E W S 9
an intention-to-treat analysis. By the end of the
study, index participants had 10,031 person-
years of follow-up, while partners were followed
for 8,059 person-years.
During the trial, researchers observed 78
HIV-1 infections among partners (annual inci-
dence, 0.9 percent; 95 percent CI, 0.7 to 1.1).
Viral-linkage status was determined for 92 per-
cent of the partner infections. Of these, 3 were
linked in the early-ART group and 43 in the de-
layed-ART group (incidence, 0.5 percent; 0.4 to
0.7), while 16 were unlinked in the early-ART
group and 12 in the delayed-ART group (inci-
dence, 0.3 percent; 0.2 to 0.4). [N Engl J Med
2016;doi:10.1056/NEJMoa1600693]
Early initiation of ART was associated with a
93 percent reduced risk of linked partner infec-
tion, compared with delayed ART (hazard ratio,
0.07; 0.02 to 0.22). No linked infections were
observed when HIV-1 infection was stably sup-
pressed by ART in the index participant.
Recent reports have shown that very early
initiation of ART can preserve immune function
and reduce complications of HIV-1 infection. In
our study, the early initiation of ART also provid-
ed health benefits to the participants receiving
treatment, said researchers.

Hypothyroidism increases NAFLD risk
JAIRIA DELA CRUZ
P oor thyroid function may increase the risk of
non-alcoholic fatty liver disease (NAFLD),
as well as the risk of fibrosis, according to data
from the Rotterdam study.
Thyroid hormone is the major regulator of
metabolic rate. Although hypothyroidism has
been implicated in the aetiology of NAFLD, pri-
or studies regarding the association between
thyroid function and NAFLD risk have yielded
controversial results, varying from a strong
to no association, said one of the investiga-
tors, Dr. Layal Chaker from the Erasmus MC
University Medical Center in the Netherlands.
To address this issue, Chaker and his col-
leagues looked at baseline thyroid function
measurements and NAFLD data of 5,324 indi-
viduals (mean age 64.75 years; 56.5 percent
female). Thyroid function was evaluated using
free thyroxine (FT4), thyroid-stimulating hor-
mone (TSH), and thyroid peroxidase antibodies
(TPOAb). Follow-up time was 10.04 years on
average.
Incident hepatic steatosis occurred in 1,763
participants, accounting for 1,217 cases of inci-
dent NAFLD. Transient elastography was used
to determine the presence of fibrosis (defined
as liver stiffness [LS] 8 kPa). [J Clin Endocrinol
Metab 2016;doi:10.1210/jc.2016-1300]
FT4 levels were negatively associated with
NAFLD risk (adjusted odds ratio [aOR], 0.42;
95 percent CI, 0.28 to 0.63). Individuals with the
lowest FT4 levels were 1.31 times (1.11 to 1.56)
AUGUST 2016 N E W S 10
as likely as those with the highest FT4 levels to
develop NAFLD.
On the other hand, TSH levels had a positive
association with NAFLD risk (aOR, 1.07; 0.98 to
1.17). There was no significant association be-
tween TPOAb and NAFLD risk (OR, 1.09; 0.89
to 1.32).
There was a gradual and significant decrease
in the risk of NAFLD across thyroid function cat-
egories, with an OR of 2.08 for hypothyroidism
and 0.54 for hyperthyroidism. Individuals with
poor thyroid function were 1.24 times (1.01 to
1.53) as likely as those with normal thyroid func-
tion to develop NAFLD.
Of note was a similar pattern of association
observed between FT4 levels, TSH levels, and
NAFLD with fibrosis. The risk of NAFLD with fibro-
sis was greater among individuals with elevated
THS levels (OR, 1.55; 1.09 to 2.20), and was non-
significantly lower among those with elevated FT4
levels (OR, 0.41; 0.09 to 1.73).
Moreover, the risk of NAFLD with fibrosis de-
creased gradually from hypothyroidism to hy-
perthyroidism (p=0.002). Individuals with sub-
clinical hypothyroidism had 2.30-fold (1.12 to
4.31) increased odds of developing NAFLD with
fibrosis compared with euthyroid individuals.
Our findings consistently demonstrate that
low thyroid function is associated with an in-
creased risk of developing NAFLD, as well
as higher risk of having NAFLD with fibrosis.
Therefore, it can be hypothesized that a hypo-
thyroid state might accelerate the progression
of liver steatosis to fibrosis, Chaker said.

Glucocorticoid use tied to elevated
risk of S. aureus infection
ROSHINI CLAIRE ANTHONY
Individuals taking systemic glucocorticoids
appear to have more than twice the risk of
community-acquired Staphylococcus aureus
bacteraemia (CA-SAB) compared with nonus-
ers, a Danish population study claims.
Compared with nonusers, those currently
on glucocorticoids had an increased risk of
CA-SAB (odds ratio [OR], 2.48, 95 percent
confidence interval [CI], 2.12-2.90). The risk of
CA-SAB was also elevated in new glucocorti-
coid users (OR, 2.73, 95 percent CI, 2.17-3.45)
and long-term users (OR, 2.31, 95 percent CI,
1.90-2.82) compared with nonusers. The risk
was still higher, but less marked, in former
glucocorticoid users (OR, 1.33, 95 percent CI,
0.98-1.81). [Mayo Clin Proc 2016;doi:10.1016/j.
mayocp.2016.04.023]
Higher 90-day cumulative doses of glucocor-
ticoids were associated with increased CA-SAB
risk compared with nonusers (OR, 1.32, 95 per-
cent CI, 1.01-1.72 for cumulative dose of 150
mg; OR, 2.42, 95 percent CI, 1.76-3.33 for cu-
mulative dose >500-1,000 mg; and OR, 6.25,
95 percent CI, 4.74-8.23 for cumulative dose
>1,000 mg, respectively).
Current long-term glucocorticoid users with
connective tissue diseases also had an el-
evated risk of CA-SAB compared with nonus-
ers (OR, 2.12, 95 percent CI, 1.40-3.21), as did
those with chronic pulmonary disease (OR,
AUGUST 2016 N E W S 11
2.82, 95 percent CI, 2.11-3.76), while both new
and long-term glucocorticoid users with cancer
had markedly increased risks of CA-SAB (OR,
6.23, 95 percent CI, 4.21-9.23 and OR, 3.69, 95
percent CI, 2.51-5.44, respectively).
Our study provides evidence that use of
systemic glucocorticoids is associated with
considerable risk of S. aureus blood infection,
particularly among persons receiving high-dose
therapy, said lead author Dr. Jesper Smit from
the Department of Infectious Diseases, Aalborg
University Hospital and Department of Clinical
Epidemiology, Aarhus University Hospital, Den-
mark.
These results may serve as a reminder for
clinicians to weigh carefully the elevated risk
against the potential beneficial effect of gluco-
corticoid therapy. This is especially pertinent in
patients who are already vulnerable to infec-
tion, he said.

According to the authors, glucocorticoids
affect several immune system functions,
which could be one of the reasons for the
increased risk of CA-SAB in patients on system-
ic glucocorticoid therapy.
For this study, researchers from the University
Hospitals in Aarhus and Aalborg, Denmark, and
Good bacteria promote weight loss,
BMI reduction
JAIRIA DELA CRUZ
P robiotics appear to have favourable ef-
fects on body weight and body mass index
(BMI), with the effect likely becoming stronger
when therapy is prolonged or multiple probiotic
species are consumed, according to a review.
Researchers pooled data on the efficacy of
probiotic therapies from 25 trials including 1,931
participants aged >18 years. [Int J Food Sci Nutr
2016;67:571]
Probiotic consumption yielded a significant
reduction of 0.59 kg (95 percent CI, 0.30 to 0.87)
in body weight and of 0.49 kg/m (0.24 to 0.74)
2
in BMI. The effect size was larger for BMI with the
consumption of multiple species of probiotics.
On subgroup analysis, probiotic therapy du-
ration of 8 weeks was associated with a signifi-
cantly greater reduction in BMI. Another analy-
sis revealed that trials allowing inclusion of only
AUGUST 2016 N E W S 12
Cologne, Germany acquired data from popula-
tion-based medical registries in Northern Den-
mark between 2001 and 2011 and compared
2,638 adults (age 15 years) with first-time CA-
SAB and 26,379 matched controls. Individuals
on glucocorticoids were categorized as current
(new or long-term), former or nonusers.
overweight patients (BMI 25 kg/m2) showed a
greater BMI decrease.
Probiotics, such as lactobacillus and bifi-
dobacterium, show potential in lowering cho-
lesterol levels by deconjugating bile acids and
increasing their rate of excretion. Moreover, the
concomitant use of certain prebiotics that help
regulate composition and/or activity in the gut
microbiota may boost the effect of probiotics on
body weight loss and maintenance. [J Clin Di-
agn Res 2015;9:KC01KC04; Diabetes Metab J
2015;39:291303]
The findings suggest that probiotic con-
sumption promotes weight loss and BMI re-
duction. Although the resulting numbers are
minimal, a small reduction may translate to
enormous public health benefits in the context
of reducing weight-related diseases such as
type 2 diabetes and high blood pressure, the
researchers said.

76th Scientific Sessions of the American Diabetes Association (ADA), June 10-14,
New Orleans, Louisiana, US
Eye benefits of tight glycaemic
control persist over time
ELVIRA MANZANO
N early 4 years of intensive glycaemic control
in patients with type 2 diabetes (T2D) reduc-
es retinopathy progression for up to 4 years after
stopping treatment, the ACCORDION* study has
shown, a phenomenon researchers described as
a legacy effect.
The study sends a powerful message to
people with T2D who worry about losing vi-
sion, said study author Dr. Emily Y. Chew of
the National Eye Institute in Bethesda, Mary-
land, US, who presented the findings. Well-
controlled glycaemia, or blood sugar level, has
a positive, measurable, and lasting effect on
eye health.
At year 8, the lower risk of retinopathy pro-
gression in patients who had received intensive
glycaemic control in the original ACCORD**
study persisted. Diabetic retinopathy had pro-
gressed 3 or more steps on the Early Treatment
Diabetic Retinopathy Study (ETDRS) scale in
5.8 percent of patients who had received inten-
sive glycaemic treatment versus 12.7 percent
in those who had received standard glycaemic
treatment (adjusted odds ratio [aOR], 0.42;
p<0.0001). [Diabetes Care 2016;doi: 10.2337/
dc16-0024]
ACCORDION was a follow-on study of dia-
AUGUST 2016 CO N F E R E N C E COV E R AG E 13
betic retinopathy progression in 1,310 patients
who participated in the original ACCORD study.
Researchers also assessed lipid-lowering ther-
apy with fenofibrate 160 mg daily plus simv-
astatin vs simvastatin alone. However, the re-
duced retinopathy progression previously seen
with fenofibrate in the ACCORD study did not
persist in ACCORDION.
The researchers said the beneficial effect of
fenofibrate on diabetic retinopathy may be real,
but this effect requires continued treatment to
maintain benefit. Further studies of fenofibrate in
diabetic retinopathy are therefore warranted.
The ACCORD study randomized patients to
intensive or standard treatment for glycaemia
(A1C level <6.0 vs 7.0-7.9 percent), systolic BP
(<120 vs 140 mm Hg) and dyslipidaemia (feno-
fibrate 160 mg daily plus simvastatin or simvas-
tatin alone. Both intensive glycaemic control and
fenofibrate, but not intensive BP control an-

other aspect of the trial reduced retinopathy
progression. [N Engl J Med 2010; 363:233-244]
Our study results provide evidence that in-
tensive glycaemic control is beneficial for reduc-
ing the progression of diabetic retinopathy and
that the legacy effect is evident in people with
diabetes, said the researchers. The addition
of the ACCORDION retinal results to prior find-
ings demonstrates a posttreatment benefit of in-
tensive glycaemia control on the progression of
eye, kidney and nerve disease.
Lowering blood glucose can reduce pro-
Pioglitazone reduces diabetes risk
in nondiabetic, insulin-resistant
patients
ROSHINI CLAIRE ANTHONY
P ioglitazone reduces the risk of diabetes
in nondiabetic, insulin-resistant individu-
als with cerebrovascular disease particularly
those with prediabetes, according to a study.
The Insulin Resistance Intervention after
Stroke (IRIS) trial recently demonstrated a
lower risk of stroke, myocardial infarction, and
progression to diabetes among nondiabetic,
insulin resistant patients who were on the thi-
azolidinedione drug pioglitazone compared
to those on placebo (hazard ratio [HR], 0.76,
95 percent confidence interval [CI], 0.62-0.93;
p=0.007). [N Engl J Med 2016;374:1321-1331]
AUGUST 2016 CO N F E R E N C E COV E R AG E 14
gression of retinal disease relatively late in the
course of T2D and even short-term changes in
glucose have an effect, according to a press
release from the US National Eye Institute.
However, the benefits of intensive glycaemic
therapy must be weighed against the potential
risks, particularly the increased risk of death ob-
served in ACCORD.
*ACCORDION: ACCORD Follow-On Eye Study
** ACCORD: Action to Control Cardiovascular Risk in Diabetes Eye
Study
Using the IRIS data, researchers performed
a secondary analysis to identify the effect of
pioglitazone on diabetes prevention in nondi-
abetic, insulin-resistant patients with a recent
stroke.
By 4.8 years follow-up, 3.8 percent of pa-

tients in the pioglitazone group (n=73) and
7.7 percent of patients in the placebo group
(n=149) developed diabetes (HR, 0.48, 95
percent CI, 0.33-0.69; p<0.0001). [ADA 2016,
abstract 380-OR]
The greatest absolute risk reduction (ARR)
occurred in patients with a fasting plasma glu-
cose 100 mg/dL vs <100 mg/dL (ARR, 8.5
vs 0.8 percent), HbA1c 5.7 percent vs <5.7
percent (ARR, 5.6 vs 1 percent), and Homeo-
stasis Model Assessment of Insulin Resistance
(HOMA-IR) 4.6 percent vs <4.6 percent (ARR,
6.3 vs 1.4 percent).
In almost 4,000 nondiabetic patients with
stroke or transient ischaemic attack and insu-
lin resistance [not diabetes], pioglitazone re-
duced the risk of developing type 2 diabetes
by 52 percent, and this was driven mainly by
patients who had the most deranged metabo-
lism ie, prediabetes, highest HOMA-IR levels, as
well as metabolic syndrome, said study author
Professor Silvio Inzucchi from the Yale School
of Medicine, New Haven, Connecticut, US who
presented the results.
AUGUST 2016 CO N F E R E N C E COV E R AG E 15
While the adverse event profile was consis-
tent with previous studies, Inzucchi attributed
the lack of increased risk of heart failure to the
exclusion of patients with heart failure as well
as reduction of study drug dose in patients who
developed oedema or weight gain.
Pioglitazone is now the only oral glucose-
lowering drug to reduce atherosclerotic events.
Pioglitazone is the only glucose-lowering drug
to prevent diabetes as well as improve car-
diovascular outcomes in the same trial, said
Inzucchi, who cautioned that these two find-
ings may not necessarily be linked.
Participants in the IRIS trial were 3,876 non-
diabetic patients with no prior history of dia-
betes, fasting plasma glucose <126 mg/dL,
and insulin resistance determined by HOMA-
IR >3.0, who had a recent ischaemic stroke
or transient ischaemic attack. The participants
were randomly assigned to pioglitazone 45 mg
QD (n=1,939) or placebo (n=1,937). Mean
baseline readings were 98.2 mg/dL (fasting
plasma glucose), 5.8 percent (HbA1c), 22.4
uIU/mL (insulin), and 5.4 (HOMA-IR).
 AUGUST 2016 CO N F E R E N C E COV E R AG E 16

76th Scientific Sessions of the American Diabetes Association (ADA), June 10-14,
New Orleans, Louisiana, US

Alogliptin does not increase risk

of cardiovascular death in diabetes
patients
PEARL TOH

A logliptin, a dipeptidyl peptidase-4 (DPP-4)

inhibitor, did not increase the risk of car-
diovascular (CV)-related death or nonfatal CV
events in type 2 diabetes (T2D) patients with
recent acute coronary syndrome (ACS) com-
pared with placebo, according to a post-hoc
analysis of the EXAMINE* trial.
Heart failure is a powerful predictor of mor-
tality in patients with both T2D and coronary
heart disease, said principal investigator Pro-
fessor William White from the Calhoun Cardi-
ology Center at the University of Connecticut
School of Medicine in Farmington, Connecti-
cut, US.
These findings emphasize how critical it is
to aggressively make use of evidence-based,
secondary preventive therapies in the clinical
management of patients with T2D who are at
high risk for cardiovascular disease.
Researchers found that CV-related death
rates were similar between T2D patients treat-
ed with alogliptin or a placebo (4.1 versus 4.1
percent, hazard ratio [HR], 0.85, 95 percent
confidence interval [CI], 0.66-1.10). [Diabetes
Care 2016;doi:org/10.2337/dc16-0303]
Professor Simon Heller
There was also no significant difference in
sudden cardiac deaths between the alogliptin
and placebo arms (2.2 versus 2.7 percent, HR,
0.80, 95 percent CI, 0.57-1.12).
Among all patients, 13.7 percent had at least
one nonfatal CV event, with heart attack being
the most common CV event (5.9 percent), fol-
lowed by unstable angina (3.8 percent), hos-
pitalization for heart failure (3.0 percent), and
stroke (1.1 percent).
In T2D patients with a nonfatal CV event,
those who experienced HHF had the high-
est increased risk of CV-related death (HR,
4.96; p<0.0001), followed by myocardial in-
farction (HR, 3.12; p<0.0001), stroke (HR,
3.08; p=0.011), and UA (HR, 1.66, p=0.164)

compared with patients without a nonfatal CV
event.
The EXAMINE trial randomized 5,380 T2D
patients to alogliptin or placebo within 15-90
days following an ACS, which included any
condition with blockage to the hearts blood
supply. Patients were monitored for deaths and
nonfatal CV events during a median follow-up
of 18 months.
Alogliptin, like other DPP-4 inhibitors, is de-
signed to delay the inactivation of incretin, a
class of hormones that stimulate insulin release
from the pancreas and help lower blood glu-
AUGUST 2016 CO N F E R E N C E COV E R AG E 17
cose levels.
Heart disease is the leading cause of death
in T2D patients and accounts for 50 to 80 per-
cent of deaths in diabetic people, according to
White.
So its critical we have a clear understand-
ing of the impact these medications have on
patients with T2D who are at a high risk for CV
diseases such as those involved in EXAMINE,
he said.
*EXAMINE: Examination of Cardiovascular Outcomes with Alo-
gliptin versus Standard of Care
 AUGUST 2016 CO N F E R E N C E COV E R AG E 18

Annual Congress of the European Academy of Allergy and Clinical Immunology

(EAACI) 2016, June 11-15, Vienna, Austria

Persistent urticaria symptoms

associated with urticaria activity score
ROSHINI CLAIRE ANTHONY

T he persistence of chronic spontaneous ur-

ticaria (CSU) symptoms in childhood is
associated with urticaria activity score (UAS), a
study has shown.
With the aim of investigating the aetiology
and prognosis of CSU in childhood, as well
as the factors associated with prognosis, Dr.
Ebru Arik Yilmaz from the Department of Pe-
diatric Allergy, Hacettepe University School of
Medicine, Ankara, Turkey and her colleagues
obtained and analysed data from 222 children
who were diagnosed with CSU between 1992
and 2015 at their department. Information on
current symptoms was obtained from 190 pa-
tients (85.6 percent) via telephone interviews.
[EAACI 2016, abstract 0074]
Median age at symptom onset was 8.8 years
(4.6-12.3), average age at hospital admission
was 10.1 years (6.4-13.2), UAS7 was 28 (21-
42), and median duration of urticaria was 23
months (7-48).
Almost 50 percent of patients also had an-
gioedema at admission (n=107), while 16.7
percent had concomitant allergic diseases
(n=19, 18, and 7 for asthma, allergic rhinitis,
and atopic dermatitis, respectively).
After a median follow-up of 15 months, 60
Dr. Ebru Arik Yilmaz
patients had achieved remission. The proba-
bility of remission of CSU symptoms, defined
as the disappearance of urticaria symptoms
for more than 6 months, was 10.6 percent in
1 year, 29.3 percent in 3 years, and 44.5 per-
cent in 5 years.
In a multivariate regression analysis assess-
ing factors associated with CSU persistence,
UAS7 >28 at admission was found to be a
significant risk factor for persistence of CSU
symptoms (odds ratio [OR], 6.22, 95 percent
confidence interval [CI], 1.54-25.15; p=0.01).
The probability of CSU persistence was
significantly higher in patients with UAS7 >28
compared to those with UAS7 28 [p<0.001],
said Yilmaz.
According to Yilmaz, little information
exists regarding the aetiology and natural

course of childhood CSU.
CSU is a very rare entity in childhood,
she said. To our knowledge, this is the first
study showing UAS7 as a predictive fac-
tor of prognosis of childhood CSU in a large
cohort.
Despite intensive investigation, the aeti-
ology of CSU in children remained mostly
idiopathic, said Yilmaz. The causative fac-
tor of CSU was identified in only 8.6 percent
AUGUST 2016 CO N F E R E N C E COV E R AG E 19
of patients in our cohort, she said. These
causes were identified as parasitic infection
(4.8 percent), pollen (1.5 percent), food al-
lergy (0.9 percent), urinary tract infection (0.9
percent), and Hashimotos thyroiditis (0.5
percent).
However, the natural course of childhood
CSU is favourable, with remission expected
in approximately 50 percent of patients after 5
years, she said.

Annual Congress of the European Academy of Allergy and Clinical Immunology
(EAACI) 2016, June 11-15, Vienna, Austria
Late-onset asthma common but
often underdiagnosed in the elderly
ROSHINI CLAIRE ANTHONY
T he frequency of asthma incidence in the el-
derly is similar to that in the younger popu-
lation, though the condition is often underdiag-
nosed and thus, undertreated in older people,
according to a presentation at the EAACI An-
nual Congress 2016.
Professor Vibeke Backer, chief respiratory
physician at the Department of Respiratory
Medicine, Bispebjerg University Hospital, Co-
penhagen, Denmark, said one of the reasons
behind the underdiagnosis of late-onset asth-
ma is that elderly patients seldom complain
about their symptoms as many believe that the
shortness of breath they experienced is merely
an age-related condition.
A study conducted in Colombia involving
5,539 individuals aged 40-93 years found that
asthma was underdiagnosed in 79 percent of
adults aged 64 years. [J Asthma 2015;52:823-
830] Living in the capital city (Bogota), being
female, having a higher body mass index (BMI)
or family history of asthma, and exposure to
dust particles, gases or fumes, or indoor wood
smoke were among the factors cited for the el-
evated risk in this age group, said Backer.
In the Copenhagen City Heart Study (CCHS),
the frequency of newly diagnosed asthma
AUGUST 2016 CO N F E R E N C E COV E R AG E 20
was comparable between patients aged <35
(young), 35-64 (middle-aged), and >64 years
(old). However, lung function was reduced prior
to diagnosis, with a more rapid decline in older
adults. [Respir Med 2015;109:821-827]
The elderly patients (in the CCHS) tend-
ed to have a higher incidence of shortness
of breath, though it was difficult to ascertain
whether this was due to asthma or merely be-
ing less fit than the younger patients in the
study, said Backer. Individuals >64 years had
a tendency to develop more obstruction over
a 10-year period than those aged 35, she said.
This lower lung function in the elderly was
also demonstrated in a previous study where
the FEV1/FEV was 65 percent in individu-
als aged 60-72 years, compared to 80 and
71 percent in individuals aged 18-30 and 31-
59 years, respectively (p<0.05). [Resp Med
2011;105:1284-1289]
We need to be more informed about the re-

duction of lung function and whether it is re-
duced as a result of age, or if it is specific to
asthma patients, said Backer.
The elderly face several changes that could
lead to asthma including alterations in the air-
way physiology and inflammatory profile, high-
er exposure to environmental noxiae, comor-
bidities, and deconditioning due to lower fitness
levels, said Backer.
Some of the factors that need to be taken
into account when managing an elderly asth-
ma patient include the difference in inflam-
mation (neutrophilic rather than eosinophilic)
and higher frequency of shortness of breath.
It is also important to ensure that the patient
Obesity, overweight status affect
lung function in Asian children
KATHLEEN ROSS CRUZ
C hildhood obesity and overweight status
are associated with elevated forced vital
capacity (FVC) and declined forced expiratory
volume in 1 second (FEV1)/FVC ratio in Asian
children, according to findings from the PATCH*
study.
Obesity in children is a gradually increasing
global health issue, but the relationship between
increasing weight status and lung function still
remains unclear and debatable. To determine
the relationship between the two, the research-
ers examined the impact of increasing weight
AUGUST 2016 CO N F E R E N C E COV E R AG E 21
is using inhaler accurately, and to treat co-
morbidities (eg, infections and cardiovascu-
lar disease which increase the morbidity and
mortality risk), encourage smoking cessation,
and improve patient education, she said.
As the inflammation experienced by these
patients is neutrophilic and not eosinophilic,
we probably need to manage it differently
than we do the eosinophilic cases, said Back-
er. We also need to be sure that the treatment
we have prescribed for these patients is the
right one. Due to their lower lung function,
these patients may have difficulty using their
inhalers, which we need to bear in mind, he
added.
status on lung function in Asian children.
The PATCH study comprised a population
sample of 1,717 Asian children aged 5 to 18
years. Participants age and gender-specific
body mass index (BMI) cut-off values from the

International Obesity Task Force reference were
used to define overweight and obese. Lung
function was measured with spirometry. [EAACI
2016, abstract 1211]
Of the paediatric subjects, 21.5 percent
were classified as overweight and 7.9 percent
were obese. Overweight and obese children
had significantly increased FVC than normal-
weight children, with mean difference of 39.2 mL
(p=0.026) and 58.8 mL (p=0.022), respectively,
after adjusting for confounding factors.
Overweight and obese children had sig-
nificantly decreased FEV1/FVC ratio than
Dupilumab does not alter vaccine
response in atopic dermatitis
KAVITHA G. SHEKAR
D upilumab (DPL) therapy did not impact
vaccine immune response in moder-
ate or severe atopic dermatitis (AD) patients,
said researchers. DPL efficacy and safety was
also not compromised by vaccine immune re-
sponse, they added.
The 194 patients recruited into this double-
blind placebo-controlled trial were randomized
to receive either a subcutaneous weekly injec-
tion of 300 mg DPL (a fully human monoclonal
antibody with known efficacy in patients with
moderate-to-severe AD) or a placebo for 16
weeks. At week 12, the patients were adminis-
tered one dose each of tetanus toxoid, reduced
AUGUST 2016 CO N F E R E N C E COV E R AG E 22
normal-weight children, with mean difference
of 1.17 percent (p=0.003) and 1.60 percent
(p=0.005), respectively. After adjusting for
confounders, no significant difference was
seen in FEV1, peak expiratory flow (PEF), and
forced expiratory flow at 25 to 75 percent (FEF
25 to 75) between the obese, overweight and
normal-weight children. Similarly, when chil-
dren with asthma were excluded from the
analysis, the lack of significant difference
remained.
*PATCH: Prediction of Allergies in Taiwanese Children
diphtheria toxoid, acellular pertussis (Tdap),
and quadrivalent meningococcal polysaccha-
ride vaccines. [EAACI 2016, abstract 1347]
Serum antitetanus immunoglobulin (IgG)
and meningococcal serogroup C serum bac-
terial assay (SBA) titres as vaccine responses
were measured at week 16. AD efficacy end-
points were investigator global assessment

(IGA), an improvement in eczema area and
severity index (EASI) score by 50 (EASI50)
and 75 (EASI75) percent from baseline, and
peak weekly pruritus numeric rating scale
(NRS).
Patients on DPL therapy had better IGA,
EASI50, and EASI75 scores compared with the
placebo group (44.3 versus 10.3 percent, 72.7
vs 32 percent, and 53.6 vs 19.6 percent, respec-
tively). Improved pruritus NRS score was also
seen in the DPL group as opposed to those
receiving placebo (squared mean percentage
change, -60.79 vs -27.89, respectively).
Both DPL and the placebo group had posi-
AUGUST 2016 CO N F E R E N C E COV E R AG E 23
tive antitetanus response (83.3 and 83.7 per-
cent, respectively). Similarities in SBA titre re-
sults were also observed in both the groups
(86.7 and 87.0 percent in DPL and placebo,
respectively).
Although 55.7 and 61.9 percent of patients
in the DPL and placebo group reported ad-
verse events (AE), these were relatively small
(1 AE per person) and restricted to injection
site reactions (12.4 vs 5.2 percent), upper re-
spiratory tract infections (11.3 vs 14.4 percent),
conjunctivitis (8.2 vs 0 percent), headache (5.2
vs 3.1 percent), and nasopharyngitis (4.1 vs
5.2 percent).

Annual Congress of the European Academy of Allergy and Clinical Immunology
(EAACI) 2016, June 11-15, Vienna, Austria
Allergic rhinitis apps could help patients
and doctors communicate better
RADHA CHITALE
T wo complementary mobile applications
that let patients with allergic rhinitis log their
symptoms for their physicians to follow received
favourable reviews from participants at the 2015
European Academy of Allergy and Clinical Im-
munology (EAACI) Congress, according to re-
sults of a delegate survey presented at this years
congress, held recently in Vienna, Austria.
The Allergy Diary and Allergy Diary Com-
panion apps offer many benefits to both pa-
tients and physicians, said researcher Dr.
Claus Bachert of the University of Gent in Gent,
Belgium. By using a common and cross-disci-
plinary control language, these apps will sim-
plify and improve allergic rhinitis management
[and] both physicians and patients will benefit
from a simple and rapid assessment of disease
control and medication record.
One hundred and seventeen delegates from
over 27 countries completed the survey about
the apps during the 2015 congress. Most re-
spondents were allergists but the group includ-
ed ear, nose, and throat doctors, nurses, and
pharmacists. [EAACI 2016, OAS 9]
The apps integrate the patient- and technol-
ogy-driven 2015 clinical decision support sys-
tem guidelines for allergic rhinitis. Key compo-
AUGUST 2016 CO N F E R E N C E COV E R AG E 24
nents of the apps were standardized between
the patient and physician versions, such as an
identical visual analogue scale, as well as sim-
ple language to describe the disease.
Thats a situation where the patient and the
doctor speak the same [simple] language... easy
to understand and easy to answer, Bachert said.
Among the respondents, 89.4 percent
thought the Allergy Diary visual analogue scale
was easy to use and interpret versus 4.8 per-
cent who disagreed and 5.8 percent who did
not know. Seventy-seven percent thought the
app would improve patient-physician commu-
nication though 10.1 percent did not agree and
12.8 percent did not know.
The most useful patient management fea-
tures of the Allergy Diary app were symptom
profiling, severity assessment, and allergic rhi-
nitis control assessment, followed by the medi-
cation record and graphic visualization.

The symptoms of the patients are readable
to the doctor every day. Its very easy, without
a lot of questions, the doctor immediately sees
what symptoms, how severe is the disease, is
it controlled and how controlled, and what did
the patient actually use for medication, Bach-
ert said, making it easy for the doctor to cor-
rect treatment immediately, assuming the pa-
tient filled out their app honestly.
Respondents believed filling in the app daily
would serve to remind patients to comply with
their treatments and overall, they rated the app
useful. Bachert noted that after some time, phy-
sicians could see if the allergic rhinitis treatment
Nasal microbiota could be different
in rhinitis infants
PEARL TOH
I nfants with persistent rhinitis have a higher
abundance of Actinobacteria, especially Co-
rynebacterium spp., in their nasal microbiome
compared with healthy controls, according to a
Singapore-based study.
The dynamic establishment of the nasal mi-
crobiota in early life [can] influence local mu-
cosal immune responses and the susceptibility
to develop rhinitis in childhood, said principal
investigator Dr. Lee Bee Wah from the Depart-
ment of Paediatrics at the National University of
Singapore, Singapore.
If we understand this, we might be able to
AUGUST 2016 CO N F E R E N C E COV E R AG E 25
was effective via the apps.
Though the majority of respondents (77.6)
said they planned to use the Allergy Diary Com-
panion in their practice, 10.2 percent said they
would not. Those who would not use it said so
primarily because they did not have iPads (36.4
percent), that the system was too complicated
(22.7 percent), and that they did not have time
(13.6 percent; 17.3 percent cited other reasons).
However, Bachert said it is the doctors job
to be up to date with equipment and communi-
cations systems. He said the apps are distrib-
uted in 20 countries currently, with China next
on the list.
develop strategies to prevent onset of inflam-
matory respiratory diseases.
The pilot study recruited 19 infants (10 with
persistent rhinitis and 9 healthy controls) from

the GUSTO* birth cohort. Nasal swab samples
collected from 3 weeks to 18 months of life were
analysed for bacterial DNA. [EAACI 2016, ab-
stract 1463]
The most abundant bacteria present in the
swabs belonged to the Proteobacteria phylum
(40 percent), followed by Firmicutes (30 per-
cent) and Actinobacteria (20 percent), with Co-
rynebacteriaceae, Aerococcaceae and Morax-
ellaceae being the major dominant families in
the nasal microbiota.
Longitudinal analysis of nasal swab samples
from 3 weeks to 18 months of life revealed that
rhinitis infants had more abundant Actinobacte-
ria [coefficient(B), 0.09, 95 percent confidence
interval [CI], 0.04-0.14; p<0.001] and less
abundant Staphylococcaceae [coefficient(B),
-0.03, 95 percent CI, -0.04- -0.01; p<0.001] than
healthy infants.
At the genus level, Corynebacterium was
significantly more abundant in rhinitis infants
(25.5 percent) than in healthy controls (0.7
percent) at 3 weeks of life (p< 0.05).
This pilot study suggests that the estab-
AUGUST 2016 CO N F E R E N C E COV E R AG E 26
lishment of the nasal microbiota may differ
between healthy infants and those who de-
velop rhinitis in the first 2 years of life, said
Lee. Actinobacteria, especially Corynebac-
terium spp., appears to be a key microbiota
biomarker that may increase the risk of devel-
oping rhinitis in early life.
Previous studies suggested that body micro-
biota composition was a major factor affecting
general health and disease, and also a poten-
tial regulator of inflammation, which could con-
tribute to development of chronic rhinosinusitis
(CRS). [Nature 2007;449:804-810; Cell Host Mi-
crobe 2008;4:337-349; J Allergy Clin Immunol
2011;127:1097-1107]
Another separate study analysing na-
sal swabs from 56 CRS patients showed that
among the 27 patients who underwent endo-
scopic sinus surgery, those with a more diverse
nasal microbiota and more abundant Actino-
bacteria had better outcomes. [J Allergy Clin
Immunol 2015;36:334-342]
*GUSTO: Growing Up in Singapore Towards healthy Outcomes
 AUGUST 2016 CO N F E R E N C E COV E R AG E 27

Annual Congress of the European Academy of Allergy and Clinical Immunology

(EAACI) 2016, June 11-15, Vienna, Austria

Comorbid allergy and immune factors

predict revision surgery in chronic
rhinosinusitis
PEARL TOH

C omorbid allergy and high tissue interleukin-5

(IL-5) levels were predictive of the need for
revision surgery in chronic rhinosinusitis patients
with nasal polyposis (CRSwNP) who had under-
gone endoscopic sinus surgery (ESS) previously,
reported Belgian researchers.
Long-term control of CRSwNP is a chal-
lenge despite medical treatment and ESS,
said principal investigator Dr. Philippe Gavaert,
an otorhinolaryngology specialist at the Depart-
ment of Otorhinolaryngology at the University of
Ghent in Ghent, Belgium.
The study concludes that patients with
CRSwNP regard functional ESS as a beneficial
procedure to improve their general well-being,
despite the relapsing character of the disease
and the high proportion of patients with a need
for revision surgery.
The prospective cohort study recruited 47
CRSwNP patients who were characterized clini-
cally before undergoing functional ESS and
followed-up at 6 and 12 years after surgery. [J
Allergy Clin Immunol 2016, abstract AB238]
Twelve years after primary ESS, the 38 pa-
tients who completed follow-up had significant-
Dr. Philippe Gavaert
ly better symptom score, in terms of improved
sense of smell (p=0.006) and nasal obstruc-
tion (p<0.001) compared with before surgery.
Nasal polyp score (NP score) was signifi-
cantly lower 12 years after surgery compared
with before surgery (p<0.001). Additionally, to-
tal symptom score was higher in patients with
comorbid asthma compared with those without
asthma (p=0.016).
Within 12 years after primary surgery, 78.9
percent of patients developed recurrent nasal
polyps, out of which 36.8 percent underwent
subsequent revision surgery.
[This suggests] that not every NP recur-
rence has to be followed by a functional ESS
reintervention and that surgery is not always in-
dispensable to obtain subjective well-being in
 AUGUST 2016 CO N F E R E N C E COV E R AG E 28

CRSwNP, said Gavaert. ESS were significantly higher in patients who

More patients who required revision surgery
had comorbid allergy compared with those who
did not have revision surgery (78.6 vs 37.5 per-
cent; p=0.014).
Patients with comorbid asthma or aspirin
sensitive asthma also had a higher NP score,
although this was not significantly different than
those without.
Tissue IL-5 levels measured before primary
underwent additional revision surgery com-
pared with those who did not require revision
surgery (p=0.029).
IL-5 mediates inflammation by recruiting and
activating eosinophils, which contribute to the
pathophysiology of nasal polyps, according to
Gavaert, suggesting this as a reason why IL-5
levels were predictive of the need for revision
surgery in CRSwNP patients.

Omalizumab facilitates asthma control

in obese patients
JAIRIA DELA CRUZ

O malizumab shows therapeutic potential

in severe asthma, yielding significant im-
provements in forced expiratory volume in 1
second (FEV1) and reductions in inhaled cor-
ticosteroid dose in obese compared to non-
obese patients, according to a study.
Researchers looked at 34 omalizumab-
treated patients with severe asthma (mean age
52 years; 25 female), of whom 19 were obese
(mean BMI 33.4 kg/m2) and 15 were non-
obese. Treatment efficacy was evaluated us-
ing asthma control test (ACT) score, FEV1, and
daily inhaled budesonide or equivalent mainte-
nance dose at baseline, 4 months, and 1 year
of treatment. Mean monthly omalizumab dose ter in the obese group than in the nonobese
was 383 mg. [EAACI 2016, abstract 1158] group. In obese patients, ACT increased signif-
Asthma control with omalizumab was bet- icantly from 10.5 to 23.2 at 4 months (p<0.05)

and to 24 at 1 year (p<0.05). Meanwhile, FEV1
showed greater improvements from 53.9 to
62.3 percent at 4 months (p=0.022) to 65.6
percent at 1 year (p=0.001). Mean budesonide
dose decreased from 1509.5 to 1132.6 g/
day at 4 months (p=0.011) to 665.5 at 1 year
(p=0.002). However, FEV1 at 1 year was statisti-
cally lower in obese patients than in non-obese
patients (65.6 vs 82.8 percent; p=0.020).
There were no reports of treatment-related
adverse events. Omalizumab was well-tolerated.
The findings demonstrate the efficacy and
safety of omalizumab in obese patients with
inadequately controlled severe asthma, the
researchers said.
Asthma is a common chronic disease, af-
fecting roughly 300 million people globally and
occasionally resulting in substantial morbidity
and mortality. Severe asthma occurs in about 5
to 10 percent of asthma cases and remains in-
adequately controlled even with optimized thera-
ICS duration, dose may affect body
composition in asthma patients
PEARL TOH
L onger duration and higher dose of inhaled
corticosteroids (ICS) were associated with
higher body fat composition and body mass
index (BMI) in asthma patients, according to
two studies.
The first study measured body composi-
AUGUST 2016 CO N F E R E N C E COV E R AG E 29
pies, leading to higher rates of healthcare utiliza-
tion and greater economic cost.
Obesity may negatively influence asthma
severity and control as mediated by the physi-
ologic and mechanical impact of adiposity on
lung function and airway changes. Increased
accumulation of lipids around the chest wall or
abdomen reduces total lung capacity and expir-
atory reserve volume. Consequently, a smaller
functional residual capacity promotes airway
closure and ventilation/perfusion mismatch as
a result. [Asthma Res Pract 2015;doi:10.1186/
s40733-015-0001-7]
Omalizumab is a humanized antibody that
inhibits IgE-dependent antigen presentation,
mast cell/basophil degranulation, and eosino-
phil infiltration. The agent also reduces expres-
sion of FcRI, helping to protect against allergic
airway inflammation, as well as related asthma
symptoms and aggravations. [J Asthma Allergy
2011;4:4959]

tion parameters such as BMI, body fat mass,
muscle mass, percentage body fat, and waist-
hip circumference of 90 children (45 with mild
persistent asthma and 45 healthy individuals).
Questionnaires on fast food consumption, ex-
ercise and time spent viewing the television
or computer were included. [EAACI 2016, ab-
stract 1180]
The duration of fluticasone propionate ICS
treatment in asthmatic children was positively
correlated with body fat mass (Spearmans rho,
0.435; p< 0.01), body fat percentage (Spear-
mans rho, 0.316; p< 0.05), and hip circumfer-
ence (Spearmans rho, 0.467; p< 0.001).
The researchers also found that asthmatic
children spent significantly longer hours viewing
the television or computer, consumed fast food
more often, but exercised less than healthy con-
trols (p< 0.05 for all).
Asthmatic children should be encouraged
to increase physical activity and decrease
duration of television/computer viewing,
said lead author Richard Pacheco from the
Division of Clinical Immunology and Allergy,
University of So Paulo in So Paulo, Brazil.
However, body composition param-
eters as well as waist-hip circumference
were comparable between both ICS chil-
dren and control groups, indicating that ICS
use per se might not affect body composi-
AUGUST 2016 CO N F E R E N C E COV E R AG E 30
tion but rather, the duration of use was cor-
related with an increase in body fat and hip
circumference.
Another separate retrospective study anal-
ysed data based on medical records of 97 asth-
matic adults (mean age 54.9 years) who were
on ICS with or without long-acting bronchodila-
tor (LABA) and had been followed-up for an av-
erage of 10 years. [EAACI 2016, abstract 1190]
The patients were categorized into group A
(ICS dose 800 g/day) or group B (ICS dose
>1000 g/day) and assessed on pulmonary
function and BMI from 2010-2014.
Of all patients on ICS, 88.7 percent were
also on LABA, and 84.5 percent had severe
asthma. ICS dose in group A ranged from
685-895 g/day while that in group B ranged
from 1305-1677 g/day.
Compared with group A patients, those in
group B had a longer duration of asthma (25.3
versus 33.6 years) and a lower spirometric val-
ues, despite the dose in group B being double
that of group A.
Among group B patients, an ICS dose re-
duction of 400 g/day was associated with a
10.6 percent decrease in the proportion of pa-
tients having BMI 30 kg/m2.
Decreasing ICS dose is associated with
lower BMI in patients with asthma, the
researchers said.
 AUGUST 2016 I N P R AC T I C E 31

Managing osteoporotic spinal

fractures in primary care
Spinal fractures are often the result of underlying osteoporosis. Appropriate treatment
for patients with osteoporosis is critical in preventing such fractures, but once they
occur, physicians must be prepared to identify and manage them. Radha Chitale spoke
with Dr. Hee Hwan Tak, medical director and senior consultant at the Pinnacle Spine
& Scoliosis Centre at Mount Elizabeth Medical Centre, Singapore, about managing
osteoporotic spinal fractures in primary care.

O steoporosis is a common underlying

cause of fractures, including spinal frac-
tures. Primary care physicians who have pa-
tients with osteoporosis or who are at risk for
osteoporosis under their care must be ready
to identify low back injuries and fractures, as
well as manage, treat, and make appropriate
referrals.
Patients with osteoporosis are prone to frac-
tures due to weakened and brittle bones, and
these frequently occur in the spine. The most
common area of spinal involvement for osteo- tion or trauma. Patients are more likely to com-
porotic fractures is at the junction between the plain of a sprain or pain, and might not recall a
thoracic spine and lumbar spine. This is due to specific fracture-inducing event.
the transition from a relatively stiff portion of the In any instance of spinal injury, GPs should
spine to a relatively mobile part of the spine. conduct a look, feel, and move examination
Such fractures are more likely to occur in wom- of the patient. Looking involves thorough in-
en over 50 years old who have history of osteo- spection with proper patient exposure. Feeling
porosis and may have been diagnosed as such involves palpating the spine for areas of ten-
with bone mineral density scans. derness, swelling and pain, which would indi-
cate trauma, and larger than normal gaps be-
Identifying osteoporotic spinal fractures tween the vertebrae, which suggest soft tissue
The mechanism of injury can be telling for di- disruption.
agnosing osteoporotic spinal fractures because Moving involves patient movement on his or
it is likely minor, without excessive violent mo- her own, and is a good demonstration of spinal
 AUGUST 2016 I N P R AC T I C E 32

stability. If patients can stand and walk without

much problem, it is likely a minor and stable
injury. However, if bearing weight becomes a
problem, or if a patient stands with great diffi-
culty and pain the moment they load the spine,
then the injury is likely to be unstable and more
serious.
An X-ray is required to find out what type of
X-ray of an elderly woman with a fresh osteoporotic fracture of the
injury the patient has. This may present a chal- T12 vertebra.
lenge for a physician, particularly if they only
see a few cases of spinal injury per year.
Another challenge is that other diseases can
mimic the effects of osteoporosis and cause
fractures without significant trauma. Cancers
such as multiple myeloma and tumours can
significantly weaken bones. MRI of the same elderly woman with a fresh osteoporotic fracture of
the T12 vertebra.
A comprehensive patient history with em-
phasis on the mechanism of injury helps to en-

Photos courtesy of Dr. Hee Hwan Tak.

sure proper diagnosis. An elderly woman with
low back pain and no recollection of a traumat-
ic event might indicate an osteoporotic spinal
fracture, for example.

Treating osteoporotic spinal fractures
In general, spinal injury or fracture would re-
quire swift specialist involvement. The excep-
tion would be for osteoporotic fractures, which
are more likely to be trivial, low velocity inju-
ries with background osteoporosis, and may
be treated and managed initially in an outpa-
tient family clinic with rest, pain relievers, calci-
tonin, supplementary calcium, and vitamin D.
Osteoporotic patients may still be referred for
specialist care if their condition plateaus or de-
teriorates further. A specialist consultation may
include getting an MRI to evaluate the fracture
X-ray of cement augmentation for a fresh osteoporotic fracture of
the T12 vertebra in the elderly woman. Cement augmentation will
immediately stabilize the fracture and improve the pain control and
quality of life.
age, morphology, and presence or absence of
neurological compromise. MRI is also helpful
to rule out other causes of spinal fractures, eg,
metastasis.
Proper treatment of osteoporosis can re-
duce the likelihood of spinal or other types of
fractures. Osteoporosis medications manage
the cycle of bone resorption and formation
such that the net result is greater bone forma-
tion and therefore greater bone mass.

Examples of antiresorptive drugs, which
prevent bone cells from breaking down, would
be bisphosphonates and denosumab. Bone
forming agents, which stimulate new bone cell
growth, include drugs such as teriparatide.
Treatment like teriparatide, however, must
be injected daily for 18 months compared with
denosumab, which has the advantage of being
subcutaneously injected once every 6 months
a regimen that is more likely to improve
compliance.
Follow-up care
Osteoporotic patients with spinal fractures
must be treated for their underlying systemic
disease to prevent the risk of further fragility
fractures. Pharmacological treatment should
be started in established cases of osteopo-
rotic fractures of the spine. A baseline bone
mineral density test should be ordered prior
to the commencement of drug treatment. Op-
timizing the home environment is also impor-
tant to prevent falls at home, as most osteo-
porotic fractures occur in this way.
Orthotic management is also important
as a spinal fracture reduces the length of the
spine, changing the shape and throwing it off
balance. Nowadays, there are various spinal
braces available that can help to halt the de-
terioration of the sagittal balance or kyphosis.
Furthermore, they are also more comfortable,
thereby improving the overall compliance.
AUGUST 2016 I N P R AC T I C E 33
Follow-up MRI may be needed to document
the healing of the fractures, and the likelihood
of cessation of the spinal brace.
Conclusion
Spinal fractures are common in elderly
osteoporotic patients, but GPs should use X-
ray tests and rule out cancer, tuberculosis or
bone-weakening medications to make a de-
finitive diagnosis. Minor or osteoporotic frac-
tures may only require supportive care but
more serious fractures may require specialist
intervention. Pharmaceutical intervention can
help reduce the risk of fractures in patients
with osteoporosis and aid the healing process
if they occur.
Dr. Hee Hwan Tak
Medical Director and Senior Consultant
Pinnacle Spine & Scoliosis Centre
Mount Elizabeth Medical Centre
Singapore
Online Resources
American Academy of Orthopedic Surgeons
www.aaos.org
North American Spine Society
www.spine.org
Pinnacle Spine & Scoliosis Centre
www.p-ortho.com
Asian Pacific Osteoporosis Foundation
www.apof.org
National Organization for Rare Disorders
http://rarediseases.org/rare-diseases/cushing-syn-
drome/
 MAY 2016 H U M O U R 34

Did you say you want your ashes scattered at sea?

Radiologists having fun. When?

This one over here is the new model I think lve been lucky, but then l see others
made specifically for seniors! there are luckier, and that drives me nuts!

Go back to sleep, dear. I almost forgot. You have

There are no proctologists Overbooked? Parkinsons disease, right?
under the bed!
 AUGUST 2016 R E S E A R C H R E V I E W S 35

Safe Delivery app improves quality of care in low-income

countries

T he Safe Delivery mobile app (SDA) is effec-

tive in improving the quality of health care
services in low-income countries, research has
shown.
SDA was evaluated in five rural districts of
Ethiopia. Seventy-three health care centers
were randomized to use the mobile app or the
standard of care. Perinatal mortality was evalu-
ated by monitoring 3,601 women in active la-
bor upon admission until 7 days after delivery; pared to control (mean difference 6.04 [80 per-
176 health care workers were assessed on cent] and 8.79 [107 percent], respectively). The
their knowledge and skills in neonatal resusci- SDA group had significantly better knowledge
tation at baseline and at 6 and 12 months after scores at 6 months and at 12 months.
intervention. The results provide evidence that the SDA
Perinatal mortality in the intervention cluster app could help improve healthcare delivery in
(14 per 1,000 births) was not significantly low- low-income countries where the lack of continu-
er than the control group (23 per 1,000 births; ing education remains to be a challenge.
odds ratio, 0.76).
Significant increases in the skill scores from Lund S, et al. Association Between the Safe Delivery App and Qual-

baseline were seen at 6 and 12 months in the ity of Care and Perinatal Survival in Ethiopia: A Randomized Clinical

health care workers who used the SDA com- Trial. JAMA Pediatr 2016; doi:10.1001/jamapediatrics.2016.0687
 AUGUST 2016 R E S E A R C H R E V I E W S 36

Data from industry-funded clinical trials not readily shared

C ompany sponsors of clinical trials do not

appear to be voluntarily sharing data re-
lated to their trials, according to a recent report.
To evaluate the completeness of data shar-
ing, they determined the proportion of random-
ized clinical trials registered at ClinicalTrials.gov
that were listed at the Clinical Study Data Re-
quest (CSDR) website, which is the main site
where companies voluntarily list studies from
which data can be requested. They studied all listed on the CSDR website. The proportion of
drugs other than vaccines listed on CSDR by registered trials listed on CSDR ranged from
all companies actively involved in data sharing 33 percent for Roche to 66 percent for Glaxo-
(those who had listed at least 100 studies in SmithKline. Regarding the 385 trials that re-
June 2014). ported that all documents were available, the
A total of 966 trials involving 462,751 par- number listed on CSDR ranged from 24 per-
ticipants were identified at ClinicalTrials.gov cent for Boehringer Ingelheim to 58 percent for
from the 61 drugs from 4 sponsors for which GlaxoSmithKline.
data was shared. Of these 966 trials, 512 (53
percent), involving 342,271 participants (74 Boutron I, et al. Sharing of data from industry-funded registered

percent of those involved in the studies), were clinical trials. JAMA 2016;315:2729-2730.
 AUGUST 2016 R E S E A R C H R E V I E W S 37

Analysis of mass transit microbial ecosystems useful

for biosurveillance

A nalysis of microbial ecosystems present in

mass transit systems could provide an ear-
ly warning system for the emergence of public
health threats such as antibiotic resistance, say
US-based researchers.
They collected samples from the Boston
subway system by swabbing seats and seat
backs, walls, vertical and horizontal poles, and
hanging grips inside train cars from three sub-
way lines as well as from the touchscreens and
walls of indoor and outdoor ticketing machines
at five subway stations. The samples were then screens. Surprisingly, the researchers did not
analysed using 16S amplicon and shotgun identify the mass transit system as a reservoir
metagenomic sequencing. of antimicrobial resistance or virulence genes.
The type of surface sampled was found to They suggest that their findings can be used
be a greater determinant of microbial commu- as a baseline for further testing and that any
nity structure than geographical location. All future deviations could act as an early warning
surfaces were dominated by human skin and system for monitoring public health.
oral commensals such as propionibacterium,
corynebacterium, staphylococcus, and strep- Hsu T, et al. Urban transit system microbial communities differ by

tococcus. Generalist taxa not associated with surface type and interaction with humans and environment. MSys-

humans were especially abundant on touch- tems; doi:10.1128/mSystems.00018-16

 AUGUST 2016 R E S E A R C H R E V I E W S 38

Zika virus vaccine a feasible proposition

R apid development of a safe and effective

vaccine against the Zika virus (ZIKV) ap-
pears to be a feasible proposition as preclinical
studies have shown that two different vaccine
candidates provided complete protection in
mice.
Researchers tested a DNA vaccine and
a purified inactivated virus vaccine against a
ZIKV strain from Brazil that has previously been
shown to cross the placenta and induce foetal
microcephaly and other congenital malforma- The researchers noted that similar anti-
tions. Groups of Balb/c mice received a single body-based correlates of protection have
50 g intramuscular dose of each vaccine and been reported for other flavivirus vaccines
then vaccinated and sham-control mice were that have been successful in humans. They
exposed to the virus 4 weeks after vaccina- are optimistic that a safe and effective ZIKV
tion. All mice that received a treatment vaccine vaccine is a feasible proportion and clini-
were protected from infection whereas control cal trials of the vaccines used in the ex-
mice were not. The immunized mice remained periments are expected to begin later this
protected when they were challenged again 8 year.
weeks after vaccination. Related experiments
revealed that the protective effects were clearly Larocca RA, et al. Vaccine protection against Zika virus from Brazil.

mediated by vaccine-specific antibodies. Nature 2016;doi:10.1038/nature18952.

 AUGUST 2016 R E S E A R C H R E V I E W S 39

Hip defects linked to osteoarthritis progression

G rade 2 defects in both sexes and grade 1

defects, mostly in men, are linked to clini-
cal, demographic, and structural factors relevant
for osteoarthritis (OA), suggests a study. Hip car-
tilage damage could also cause rapid disease
progression and pathophysiology of hip defects.
To describe the correlates of hip cartilage
defects, investigators conducted a cross-sec-
tional study involving 194 subjects from the
Tasmanian Older Adult Cohort who had right
hip short-tau inversion recovery magnetic res-
onance imaging (MRI).
Hip cartilage defects were assessed and
categorized as grade 0=no defects, grade
1=focal blistering or irregularities on carti-
lage or partial thickness defect, and grade Grade 1 defects were associated with hip
2=full thickness defect. Hip pain, and hip ra- bone marrow lesions (BML; PR 1.42; 1.03 to
diographic OA were assessed. Hip structural 1.96) and high cartilage signal (men; PR, 1.84;
changes were measured on MRI. Leg strength 1.27 to 2.7), but not with hip pain or other struc-
and physical activity were also assessed using tural findings. Grade 2 defects were associated
dynamometer and pedometers, respectively. with greater hip pain (PR 1.4; 1.09 to 1.8), hip
Of the participants, 24 percent had no de- BML (PR 1.45; 1.15 to 1.85), hip effusion cross-
fects, 34 percent had grade 1, and 41 percent sectional area (PR 1.14; 1.01 to 1.3), hip ROA
had grade 2 defects. In multivariate analyses, (men; PR 1.6; 1.13 to 2.25), and steps/day (PR
any hip defects were associated with greater 0.97; 0.96 to 0.99).
hip pain (prevalence ratio [PR], 1.2; 95 percent
CI, 1.02 to 1.35) and lower mean leg strength Ahedi HG, et al. Correlates of Hip Cartilage Defects: A Cross-sec-

(men; mean ratio 0.83; 0.67 to 0.98). tional Study in Older Adults. J Rheum 2016;43:1406-1412.
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