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APRIL ISSUE Senior Editor

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4 HCWs among COVID-19 patients, private hospitals committed to assist Pank Jit Sin

6 Handbook on prevention, treatment of COVID-19 now available Contributing Editors

Hong Kong: Christina Lau
Malaysia: Rachel Soon
7 Hypertension in younger Asian population Singapore: Elvira Manzano, Audrey Abella,
Roshini Claire Anthony, Pearl Toh,
Dr Margaret Shi, Natalia Reoutova
8 FDA emergency approval granted for 5-minute SARS-CoV-2 point-of-care test Philippines: Stephen Padilla, Jairia Dela
Cruz, Elaine Soliven
10 Tocilizumab and Covid-19 testing: Roche in the limelight
Designers
Razli Rahman, Tina Ng,
12 Oral appliances: A more convenient option for OSA? Peggy Tio, Sam Shum

Production
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14 Universiti Malaya inks MoU on mental health with pharma, launches mental Circulation Executive
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3
DOCTOR | APRIL ISSUE

HCWs among COVID-19 patients, private
hospitals committed to assist
RACHEL SOON
T
wenty-four healthcare workers
(HCWs) are among the current
active coronavirus disease 2019
(COVID-19) cases in Malaysia as of 21
March, with two in intensive care.
This is an increase from the 15
cases among HCWs (12 public, 3
private) reported by the MOH on the
preceding day.
In an interview with the Malay Mail,
MOH Director-General Datuk Dr Noor
Hisham Abdullah said that investiga-
tions revealed all cases of HCWs in-
fection were due to close contact with
the first and second generations of
the Masjid Jamek Sri Petaling tabligh
congregation, and not due to failure
to adhere to protective measures.
[https://www.malaymail.com/news/
malaysia/2020/03/21/health-ministry-
19-public-five-private-health-workers-
hit-with-covid-19/1848737]
“This virus knows no boundaries,
regardless of your race, religion or
wealth status, even more so if you are
a healthcare worker at the frontline of
this war,” said Noor Hisham in a public
Facebook post dated 20 March. “Our
simple message to the public today:
please help us to help you. Stay at
home.”
The news comes on the fourth day
of the national Movement Restriction
Order which has seen much of the
country’s social and economic activi-
ties put on hold to reduce social inter-
actions which may spread the disease.
HCWs have been one of the ma-
jor groups at risk in countries dealing
with COVID-19. In Italy, the current
epicentre of the global pandemic,
a reported 2,629 HCWs have been
MALAYSIA FOCUS
infected by COVID-19, represent-
ing 8.3 percent of the country’s total
cases. [https://www.aljazeera.com/
news/2020/03/rising-number-medical
-staff-infected-coronavirus-italy
-200318183939314.html]
At the time of writing, the num-
ber of COVID-19 cases in Malaysia
stands at 1,061 active cases under
treatment, with 114 additional patients
discharged and 8 deceased.
Private hospitals committed
to fight despite PPE
shortages
Malaysia’s largest association of pri-
vate healthcare providers has de-
clared its readiness to help the MOH in
COVID-19 efforts.
“The Association of Private Hos-
pitals of Malaysia (APHM), through its
member hospitals, is ready to work
with the Ministry of Health Malaysia
in managing the current surge of cas-
es of COVID-19,” said Datuk Dr Kul-
jit Singh, APHM president, in a press
statement dated 16 March.
He added that strategies and
recommendations for public-private
partnership in managing the national
COVID-19 situation are in the works
through meetings between the MOH
and healthcare providers, as well as
between APHM and its member hos-
pitals.
The APHM represents more than
140 private hospitals in Malaysia and
includes networks such as Columbia
Asia, Gleneagles, KPJ, Pantai, Sime
Darby, and Sunway, as well as special-
ist centres such as the National Heart
Institute and those of several university
hospitals.
In the same statement, Kuljit also
stressed the urgency of addressing
4
DOCTOR | APRIL ISSUE
the personal protective equipment
(PPE) supply shortage currently affect-
ing private hospitals as well.
“Private hospitals are unable to
source for three-ply and N95 face
masks and personal protective equip-
ment. It is a serious situation which
impacts the safety of patients and staff
involved,” said Kuljit. “Local manufac-
turers continue exporting such items
while private hospitals are crying out
for supplies. It’s time the MOH and
the Ministry of Domestic Trade and
Consumer Affairs (KPDNHEP) work
together to address this.”
As of 17 March, the export of face
masks from Malaysia has been halted
by the KPDNHEP under the Control
of Supplies (Prohibition on Export)
(Amendment) Regulations 2020. Par-
ties who fail to comply with the reg-
ulations may be penalized with fines
up to RM500,000, jail terms of up to
3 years, or both. [https://www.malay-
mail.com/news/malaysia/2020/03/17/
minister-bans-malaysia-from-export-
ing-face-masks/1847543]
Ed: As of 26 March, 80 HCWs have
been diagnosed with COVID-19.
The DG revealed that none of those
cases were contracted in the line
of duty. Hospital Teluk Intan is the
hardest hit with 39 affected due to
participation in a wedding event.

Handbook on prevention, treatment of
COVID-19 now available
PANK JIT SIN
A
handbook on the prevention
and treatment of coronavirus
disease 2019 (COVID-19) has
been released by The First Affiliated
Hospital, Zhejiang University School of
Medicine (FAHZU), China.
The handbook is the result of the
Global MediXchange for Combat-
ing COVID-10 (GMCC) programme,
which is a platform to facilitate contin-
ued communication and collaboration
across borders, and to provide the
necessary computing capabilities and
data intelligence to empower import-
ant research efforts, which are in turn
provided by Alibaba Cloud Intelligence
and Alibaba Health.
The 68-page open access e-book
can be downloaded at https://
covid-19.alibabacloud.com/. It is di-
vided into three main parts: preven-
tion and management; diagnosis and
treatment, and nursing. It comes with
a caveat, though, that the information
may not be absolutely correct due to
MALAYSIA FOCUS
the hurried nature of publication and
information collation, noted the editor
Professor Tingbo Liang, Chairman of
FAHZU.
The book contains comprehen-
sive guidelines and best practices for
coping with COVID-19 and explains
the necessity for hospitals and other
healthcare institutions to have com-
mand centres when faced with a
large-scale emergency, in the context
of the coronavirus pandemic. Import-
ant topics covered include technical
strategies for addressing issues during
emergencies; treatment methods for
the critically ill; efficient clinical deci-
sion-making support; and best prac-
tices for departments such as outpa-
tient clinics.
The effort was supported by the
Jack Ma Foundation and Alibaba
Foundation based on the virtue of re-
source sharing and the understanding
that the virus cannot be beaten unless
all stakeholders share their resources,
know-how, and experience.
6
DOCTOR | APRIL ISSUE
The Jack Ma Foundation, founded
in 2018, is a philanthropic organization
with emphasis on improving aspects
of education, the environment, and
public health. Meanwhile, the Alibaba
Foundation, established in 2011, is a
private charity fund that emphasizes
on environmental protection in China
and empowering the disadvantaged.
[Available at https://alibabagroup.
com/en/about/sustainability Accessed
on 19 March]
This isn't the only COVID-19 re-
lated effort to be funded by the Jack
Ma Foundation, as the body also
announced its intention to donate
500,000 test kits and 1 million face-
masks to the US.
SCAN
QR Code

Hypertension in younger Asian population
PANK JIT SIN
T
he rate of hypertension is in-
creasing among the young, but
their awareness and treatment
rates remain low, says a Korean car-
diologist.
Dr Jinho Shin, a cardiologist at
the Department of Internal Medicine,
Hanyang University College of Medi-
cine, South Korea, said hypertension
among the younger population (those
aged between 30 and 49 years) is an
emerging problem in South Korea. The
problem isn’t so much an increase in
hypertension but the low awareness,
treatment and control rates in this
population.
To circumvent the lack of aware-
ness in the younger population, Shin
advocates an active screening pro-
gramme targeted at them. For ex-
ample, the May Measurement Month
(MMM) programme and the Hyperten-
sion Awareness Week can be used
for this endeavour. Shin was speaking
to the participants at the 17th Annual
Congress of the Malaysian Society of
Hypertension, held in Kuala Lumpur,
recently. Shin, who presented via a
recording due to his country’s travel
restriction, said the awareness rate of
younger patients is only half of the el-
derly (those aged 50 and above).
Of the number who are aware of
their hypertensive situation, only half
are treated, with an overall control rate
of less than 20 percent. Even in those
who are aware of being hypertensive,
about a quarter are still insufficiently
treated. However, Shin noted that the
control rate is similar to those in the
older population. In light of these fac-
tors, Shin said a strategy to increase
awareness among the younger popu-
lation is needed.
Compounding the situation of low
MALAYSIA FOCUS
awareness among the younger group
of patients about their hypertensive
condition is their poor adherence to
medication.
In the younger group of patients,
lifestyle changes are essential and ef-
fective in lowering blood pressure (BP).
In order to improve the treatment rate
and adherence in younger patients,
Shin said empathic and motivational
strategies go a long way. By establish-
ing a rapport with these patients, and
expressing empathy to their situation,
a doctor is more likely to get the pa-
tient to work towards an agreed target
or behavioural change.
Hypertension and atrial
fibrillation, the dreaded duo
In a separate lecture, Dr Suraya Hani
Kamsani, cardiologist at the National
Heart Institute (IJN), Kuala Lumpur,
also spoke about the link between hy-
pertension and atrial fibrillation (AF) in
a relationship that can be described
as a marriage of inconvenience. The
two conditions are described as such
because the two are incompatible and
yet in many instances are welded in-
dissolubly together.
The risk factors for both hyperten-
sion and AF are similar, including obe-
sity and overweight, diabetes, sleep
apnoea, and hyperlipidaemia, noted
Suraya. “In hypertension, the heart
becomes hypertrophic and endothe-
lial dysfunction causes increased risk
of heart failure with preserved ejection
7
DOCTOR | APRIL ISSUE
fraction (HFpEF), arterial stiffness and
kidney dysfunction.” What follows is
atrial stretch and fibrosis, leading to
AF. Over time, with improper rhythm
control therapy, permanent AF sets in.
The outcomes of this hyperten-
sion-AF combination are increased
risk of stroke, congestive heart failure,
major bleeding, cognitive decline, and
subsequent death.
Thus, it is imperative that hyperten-
sion should not be allowed to progress
to AF. This would necessitate tighter
BP control in those who are hyperten-
sive without diabetes. Tight BP con-
trol, especially systolic BP, has been
proven to reduce the incidence of new
onset AF. The Malaysian Hyperten-
sion Guidelines recommend a BP of
<140/90 mmHg with the elderly (aged
>75 years of age) being placed on oral
anticoagulants plus angiotensin-con-
verting enzyme (ACE) inhibitors or an-
giotensin II receptor blockers (ARBs)
to reduce mortality risk. Rate control
should be done with beta-blockers or
non-dihydropyridine calcium channel
blockers.
Meanwhile, the 2018 ESC/ESH*
guidelines for HTN patients with AF
also recommend the same com-
pounds for heart rate control as the
Malaysian guidelines but recommend
a lower systolic BP target at <130
mmHg.
* ESC/ESH: European Society of Cardiology/
European Society of Hypertension
 MALAYSIA FOCUS

FDA emergency approval granted for

5-minute SARS-CoV-2 point-of-care test
RACHEL SOON deploy the ID NOW SARS-CoV-2

T
he US Food and Drug Adminis-
tration (FDA) has issued emer-
gency use authorization (EUA)
for a molecular point-of-care SARS-
CoV-2 test that promises to deliver
results in minutes.
Developed by Abbott Labora-
tories, the test is built to run on the
company’s existing ID NOWTM test-
ing platform, a portable 3 kg machine
which can be used in physicians’ of-
fices, urgent care clinics and hospital
emergency departments, according to
a press statement by the company.
“ID NOW is a rapid, instru-
ment-based, isothermal system for
the qualitative detection of infectious
diseases. Its unique isothermal nu-
cleic acid amplification technology
provides molecular results in just min-
utes, allowing clinicians to make evi-
dence-based clinical decisions during
a patient visit,” said Abbott represen-
tatives.
In a brief video, the company ex-
plained that the test devised for de-
tection of SARS-CoV-2 focuses on
identifying a small section of the viral
genome and rapidly replicating it to
detectable levels, with positive results
delivered as rapidly as 5 minutes and
negative results in 13 minutes. [https://
www.youtube.com/watch?v=MqICk-
kOaNKo]
First released in 2014, ID NOW
machines are already in use in US
healthcare facilities for testing other
infectious diseases such as influenza
A and B, Group A streptococci, and
respiratory syncytial virus (RSV). The
company has announced it will be
working with the US government to
tests in early April to urgent care
settings across the country, with
test production being accelerat-
ed to 50,000 units per day.
“Through the incredible work
of teams across Abbott, we ex-
pect to deliver 50,000 COVID-
19 tests per day to healthcare
professionals on the front lines,
where testing capabilities are
needed most,” said Chris Scog-
gins, senior vice president,
Rapid Diagnostics, Abbott.
At the time of reporting, the Testing being performed on Abbott’s ID NOW platform.
US has the highest number of (Photo credit: Abbott Laboratories)
COVID-19 cases in the world,
with over 140,000 individuals con-
firmed positive for the virus. Globally,
cases have exceeded the 720,000
mark.
“The COVID-19 pandemic will be
fought on multiple fronts, and a porta-
ble molecular test that offers results in
minutes adds to the broad range of di-
agnostic solutions needed to combat
this virus,” said Robert B. Ford, pres-
ident and chief operating officer, Ab-
bott. “With rapid testing on ID NOW,
healthcare providers can perform mo-
lecular point-of-care testing outside
the traditional four walls of a hospital in
outbreak hotspots.”
Prior to the approval of the ID NOW
SARS-CoV-2 test, the company had
also received an FDA EUA for a test
utilizing its m2000 RealTime system,
which is used in hospitals and labora-
tories. Between the two platforms, the
company expects to produce an esti-
mated 5 million tests per month.
According to Abbott Laboratories’
director of public affairs Sharon Mak,
the ID NOW SARS-CoV-2 test is avail-
able only in the US currently as it is
where most ID NOW instruments are
located.
“Abbott is developing COVID-19
tests across our testing platforms,
including laboratory and lateral flow
tests, and plans to bring more tests
forward with the intent to get them to
more people in more places around
the world,” said Mak. “We are working
to produce as many tests as possible,
running our production 24/7 and will
expand manufacturing capacity when
we can.”
Multiple pharmaceutical and med-
ical device companies are racing to
develop rapid tests for SARS-CoV-2
as the pandemic continues to cross
the globe. On 13 March, FDA EUA
was also granted to Roche Hold-
ing AG’s rapid test on the compa-
ny’s cobas® 6800/8800 systems,
which provide results in 4 hours
and can test 1,440 to 4,128 pa-
tients a day. [https://www.thestar.
com.my/news/regional/2020/03/13/
us-approves-roche039s-
n e w - a n d - f a s t e r- c o v i d - 1 9 - t e s t ]

8
DOCTOR | APRIL ISSUE
 MALAYSIA FOCUS

Tocilizumab and Covid-19 testing:

Roche in the limelight
PANK JIT SIN

P
harmaceutical giant Roche was
recently in the news for all the
right reasons. First was the fact
that its monoclonal antibody tocili-
zumab (Actemra®) is currently being
tested in China for the treatment of
COVID-19. The second piece of posi-
tive news comes from its diagnostic di-
vision, where the Roche SARS-CoV-2
test was approved by the US FDA.

China included tocilizumab in its

National Health Commission treatment
guidelines for COVID-19, dated March
3. [Available at www.nhc.gov.cn/yzygj/
s7653p/202003/46c9294a7dfe4cef-
80dc7f5912eb1989.shtml Accessed
on 16 March] The drug was initially
indicated for treatment of rheumatoid
arthritis, and more recently, the cyto-
kine release syndrome associated with
chimeric antigen receptor (CAR) T-cell
treatment.
“Given the lack of
approved treatment
options, we
understand that there
may be off-label use
of products approved
for other uses.”
Roche donated 10,000 vials of
tocilizumab to China after Chinese
doctors revealed during a press con-
ference that promising improvements
were seen in some critically ill patients
treated with existing medications, in-
cluding those used in arthritis. One of
these was tocilizumab.
The University of Science and
Technology of China in Anhui wasted
no time in initiating a clinical trial* to re-
cruit 188 patients, half of which will be
randomized to tocilizumab plus con-
ventional therapy and the remaining
half to conventional therapy alone.
MIMS Doctor reached out to
Roche to gain more insight into the
use of tocilizumab in the treatment of
COVID-19. A Roche Medical Informa-
tion correspondent mentioned that it
was important to note that there is no
published clinical evidence regarding
the safety or efficacy of tocilizumab in
the treatment of COVID-19.
She added: “Roche is aware that
the current situation is a major burden
for patients and their beloved ones.
While there are currently no medicines
to treat human coronaviruses, Roche
remains committed to the WHO and
other relevant stakeholders as neces-
sary, to provide expertise and advice
on coronavirus. Roche is also com-
mitted to contributing to the contain-
ment of coronavirus spread through its
diagnostic solutions. The information
provided may include the use of the
product outside the product’s license.
Roche is providing this information in
response to your enquiry. We cannot
recommend the use of our products
for any indication, dosage, or route
of administration not covered in the
product’s license.”
Dr Charles Li, Medical and Reg-
ulatory Director of Roche Malaysia,
echoed the sentiments and reiterated
that no health authority apart from Chi-
na has approved tocilizumab for use
in treatment of COVID-19. He said:
“Given the lack of approved treatment
options, we understand that there may
be off-label use of products approved
for other uses.”
He added: “Roche respects the
physician’s clinical decisions, and we
believe that when a physician choos-
es to prescribe a medicine, approved

10
DOCTOR | APRIL ISSUE
 MALAYSIA FOCUS

or otherwise, they should do so be-

cause they believe it is the most appro-
priate medicine for an individual patient,
taking into account relevant national
laws and regulations.”

When doctors prescribe a medi-

cine for off-label use, they do so with
the knowledge that the product has
not gone through the stringent regula-
tory process for the specific disease in
question, so there is a greater degree
of uncertainty associated with its use.

On the possibility of Roche do-

nating supplies of tocilizumab for use
in the government setting, Li said all
such requests are handled exclusively
by the local General Manager through
direct contact with the local authorities
and aid organizations, and based on
the related needs.

over 1,400 samples a day. Each run treatment. This was suggested in a re-
“When doctors will take about 4 hours. MIMS Doctor cent paper which saw the link between
prescribe a medicine has reached out to Roche Diagnos- RNAaemia and extremely elevated
tics to see how soon the tests will be IL-6 levels in critically ill COVID-19
for off-label use, made available in Malaysia. The test is patients. [Available at https://doi.
they do so with the officially known as the Roche SARS- org/10.1101/2020.02.29.20029520 ]
knowledge that the CoV-2 test.
product has not gone Being an IL-6 receptor antagonist,
A hallmark of serious disease in tocilizumab blocks IL-6 receptors, and
through the stringent those with COVID-19, drastically ele- suppresses the immune system and
regulatory process.” vated interleukin 6 (IL-6) or otherwise subsequent inflammatory response,
famously known as the “cytokine thus possibly attenuating the serious
storm”, is thought to be a target for symptoms of COVID-19.
COVID-19 testing speeds
up
Fresh on the heels of the news on to-
cilizumab’s use in COVID-19 patients
is the announcement that Roche has
now launched a new test for the novel
coronavirus which is “10 times faster”
than existing tests. The US FDA grant-
ed emergency use authorization to the
test due to the unique and pressing
nature of the coronavirus pandemic.

The tests run on Roche’s cobas®

6800 and 8800, both of which are
available in Malaysia. The 8800 sys-
tem can test over 4,000 samples a * Trial registration number ChiCTR2000029765: A multicenter, randomized controlled trial for the efficacy
day while the 6800 system can test and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19).

11
DOCTOR | APRIL ISSUE

Oral appliances: A more convenient option
for OSA?
RACHEL SOON
O
ral appliance therapy should
be considered for patients
facing compliance issues with
CPAP* therapy for obstructive sleep
apnoea (OSA), says an expert.
According to Dr John H Walker,
clinical professor of orthodontics at
Boston University, US, patients with
OSA often do not use CPAP machines
sufficiently during sleep to prevent the
onset of potential complications from
their condition.
“We’re finding these days that
[CPAP] has to be worn at least 7 hours
a night, 7 days a week, or else it’s not
going to have any effect on the heart
… their cardiomyopathy is going to
continue,” said Walker. “If you’re wear-
ing it for 5–6 hours a night, or take it off
on weekends, it’s not going to work.”
An estimated 50 percent of pa-
tients failed to wear the masks at all in
his experience, he added.
Speaking at the recent ENT Sum-
mit 2020 in Kuala Lumpur, Malaysia,
Walker highlighted the use of oral
appliances such as mandibular ad-
vancement devices (MAD) and tongue
retainers which have shown some
benefits for patients with mild-to-mod-
erate OSA, though their effectiveness
varied depending on the location of
the obstruction in the patient’s oro-
pharynx and the form of jaw support
provided by the device.
Among the pros of oral appliance
use Walker mentioned were the rela-
tively improved comfort of nightly use
compared to CPAP masks, compact-
ness for travel, ease of cleaning at
home, and overall improved airway
hygiene.
MALAYSIA FOCUS
He added that oral appliances not
only prevented oropharyngeal col-
lapse in supine positions but could
also strengthen muscle and interstitial
tissue in the jaw over time.
“This is also still the only alterna-
tive for minimally invasive care without
maxillomandibular advancement sur-
gery for severe sleep apnoea,” said
Walker.
However, he cautioned that such
devices required expert fitting, and the
patient would have to go through ad-
ditional motor testing and 3D scanning
procedures beforehand, compared to
CPAP machines which can be more
easily issued.
Walker also admitted that the cost
of oral appliances, which require cus-
tom fitting for each patient’s dental
profile by a dentist or orthodontist,
could be prohibitive for patients. In
Walker’s private practice in the US, the
costs for oral appliances can start from
US$800 per piece at point of laborato-
ry manufacture, reaching US$2,400 at
point of care.
12
DOCTOR | APRIL ISSUE
Walker did not recommend oral ap-
pliances for young or obese patients,
as the former would need to regularly
change devices to match their growth.
In the case of the latter, oral appliances
might have limited effect on their OSA
as the source of obstruction would
more likely be the enlarged tonsil and
soft tissues in the oropharynx.
On the topic of OSA diagnostic
processes in general, Walker advised
physicians to avoid an overreliance on
CT scans to make a decision on us-
ing CPAP for patients with OSA, as CT
scans can overlook some obstructions
in the oropharynx that are more visible
only with a clinical examination.
“You have to know what the ob-
struction actually is, not just fit them
for a mask based on general symp-
toms,” said Walker, who added that
some obstructions which did not re-
spond well to CPAP or oral appliances
would require surgical interventions.
* CPAP: Continuous positive airway pressure

Choose nasal topical therapies based on
target region, patient compliance
RACHEL SOON
P
hysicians treating nasal condi-
tions should bear in mind that
different devices are better at
delivering drugs to different nasopha-
ryngeal regions, says an expert.
According to Professor Dr Michele
Cassano, assistant professor of oto-
rhinolaryngology at the University of
Foggia, Italy, topical therapies can be
attractive as they avoid systemic side
effects and increase the activity of
many drugs compared to other intake
methods, but there are many factors
that can influence their nasal and sinus
distribution.
“This study aimed
to go further in
understanding the
importance of the nasal
delivery device …”
Speaking at the recent ENT
Summit 2020 in Kuala Lumpur, Ma-
laysia, Cassano described a study
that demonstrated how the sizes of
nebulized particles affected their air-
way deposition patterns, with parti-
cles >10 μm in diameter depositing
mainly in the nose, 5–10 μm in the
sinuses, and 1–5 μm in the lower air-
ways. [Int J Immunopathol Pharmacol
2018;32:2058738418802676]
Other factors highlighted by Cas-
sano included the irrigation volume
being delivered, the necessary head
positioning and angle between de-
vice and vestibule, the negative versus
positive pressure of a nebulization de-
vice, an individual patient’s nasal and
sinus anatomy, as well as the viscosity
of the substance being delivered.
MALAYSIA FOCUS
“Irrigation-type devices can deliver
higher volumes than sprays, and may
reach a larger proportion of the nasal
cavities, but we need to be careful
about patient compliance,” said Cas-
sano, who noted that irrigating devices
such as syringes tended to be more
uncomfortable for a patient self-apply-
ing their treatment.
Cassano also highlighted a com-
parative study he conducted with a
team of colleagues in Italy using six
different nasal delivery devices on ca-
daver models. The study aimed to de-
termine the intranasal deposition pat-
terns of each device on six anatomic
regions, which included the nasal ves-
tibule, inferior and middle turbinates,
nasopharynx, nasal cavity floor, and
superior olfactory cleft. [Biomed Res
Int 2019;4602651]
The nasal delivery devices tested
in the study were the two-puff nasal
spray, 2.5 mL single-dose vial, 2.5 mL
irrigation syringe, 2.5 mL nasal Mu-
cosal Atomization Device (MAD), 2.5
mL Spray-sol and 2.5 mL Rinowash
nasal douche. The level of subsite sur-
face staining was scored by four re-
viewers using an ordinal grading scale
of 1 to 5 (1=0 to 20 percent, 5=81
13
DOCTOR | APRIL ISSUE
to 100 percent subsite surface area
stained).
Using a blue vegetable dye as a
test solution, Cassano’s team found
that nasal sprays scored below grade
2 in all six regions.
The other five devices scored be-
tween grades 2 and 5 for the nasal
vestibule, nasal cavity floor and inferi-
or turbinate, but the vial scored grade
<2 for the middle turbinate and supe-
rior olfactory cleft, while the irrigation
syringe and Rinowash performed as
poorly as nasal spray in staining the
middle turbinate and nasopharynx.
Spray-sol showed consistent
grade 3+ staining of all six regions,
while nasal MAD scored above a grade
2 for all regions except the nasophar-
ynx. “This study aimed to go further in
understanding the importance of the
nasal delivery device [in topical thera-
pies],” said Cassano.
He added that in general, topical
therapies and the delivery method of
choice should be tailored based on
the disease, severity of symptoms, as
well as the patient’s acceptable level of
cost and compliance.

Universiti Malaya inks MoU on mental
health with pharma, launches mental health
initiative
PANK JIT SIN
U
niversiti Malaya (UM) recent-
ly launched the UM Mental
Health Initiative, a platform to
push for mental health activities in
the university. The initial focus of the
initiative will be on students and the
university signed a Memorandum of
Understanding (MoU) with Johnson &
Johnson Sdn Bhd (J&J) on initiatives
to innovate teaching and learning in
healthcare. Of note is the component
on mental health, which is aligned to
the MOH’s #Letstalkmindasihat initia-
tive launched in 2019.
Those present at the signing cere-
mony were Datuk Seri Dr Dzulkefly Ah-
mad, former Minister of Health of Ma-
laysia; Chin Keat Chyuan, managing
director, J&J Malaysia; and Professor
Dr Noorsaadah Abdul Rahman, dep-
uty vice-chancellor (Research and In-
novation), Universiti Malaya. Noorsaa-
dah said the Universiti Malaya Mental
Health Initiative was started by UM’s
Community Engagement and Sustain-
ability Centre (UMCares) together with
the Student Counselling Centre, Stu-
dent Health Centre, UM Sustainability
and Living Labs Secretariat, and the
UM Faculty of Medicine, in partnership
with J&J Malaysia.
The MoU between UM and J&J
covers projects related to healthcare
which include urology, orthopaedics
and mental health. J&J and J&J In-
stitute will be helping UM to develop
teaching and learning projects online
and offline. These projects will assist
in empowering more healthcare pro-
viders to be knowledgeable and skillful
in the three areas of health. The MoU
will go beyond teaching and learning
initiatives, noted Noorsaadah, and will
MALAYSIA FOCUS
include collaboration on staff and stu- inclusion of the mental health compo-
dent development by way of internship nent will benefit the MOH and its #Let-
programmes and mutually beneficial stalkmindasihat initiative launched in
activities for both parties. October 2019. The impetus to focus
on mental health comes as a result
The focus on mental health is of the findings of the 2015 National
timely as a study published by the Health and Morbidity Survey, which
Faculty of Medicine among more than found 16 percent of youths aged
1,000 undergraduate students in UM between 10 and 19 to have mental
discovered that almost 30 percent health problems, namely depression,
experienced depression and 4.4 per- anxiety and stress. He said the minis-
cent reported severe depression, said try is aware of the trials and challenges
Noorsaadah. Among the noted risk faced by adolescents during their peri-
factors for poor mental health were liv- od of growth, hence the #Letstalkmin-
ing off campus, lower socioeconomic dasihat initiative. The objectives of the
backgrounds, poor sleeping habits, initiative are to improve mental health
and a history of post-traumatic stress awareness and reduce stigma; im-
disorder. The study highlights the ne- prove knowledge of target populations
cessity for institutes of higher learning (including youth) on mental health and
to place more attention on the mental illnesses; encourage those affected to
needs of students. seek help; and to encourage friends
and family to provide support whenev-
Chin, in his delivery, said pub- er possible.
lic-private partnerships
are key in creating the
most effective results.
“Today, I am honoured to
witness yet another mile-
stone with this MoU with
UM, which demonstrates
our commitment to forge
ever stronger public-pri-
vate partnerships in
addressing healthcare
needs of the nation …
This MoU signifies the
start of a long partner-
ship that aims to elevate
and advance our health-
care and education land-
scape in the country.
I am truly excited and
hope you are, too.”
Dzulkefly lauded the
collaboration between
UM and J&J, saying the Dzulkefly witnessing the MoU signing between UM and J&J.
14
DOCTOR | APRIL ISSUE
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 COVER STORY

COVID-19 is officially a pandemic –

the first to be caused by a coronavirus,
the WHO* declared on Mar 11.

16
DOCTOR| |MARCH
DOCTOR APRIL ISSUE
ISSUE
 COVER STORY

PEARL TOH

alling the pandemic “a global health crisis unlike any in the 75-year history

C of the United Nations [UN]”, UN Secretary-General António Guterres

highlighted that “COVID-19 is killing people, as well as attacking the real
economy at its core – trade, supply chains, businesses, [and] jobs.”1

Fallouts from the pandemic are of an unparalleled scale — cascading human

suffering, plunging economy globally, and turning people’s lives upside down.

A global recession, which Guterres believed to be possibly of “record dimensions”,

is almost a certainty.

“Our world faces a common enemy. We are at war with a virus,” he declared.

Veni, Vidi … Vici?

Within a span of 3 months, what started out as an outbreak from a seafood market
in China had treaded across 200 countries and territories around the globe, claiming
more than 37,000 lives to date along its track.

Worse still, the number of daily new cases continues to mount globally, with no signs
of abating – in particular, in the US, Iran, and certain countries in Europe such as Italy,
Spain, Germany, and France.

On Mar 16, the total number of confirmed cases outside of China hits above 83,000 –
surpassing that inside the country, the first time since the COVID-19 outbreak.

Italy, the worst-hit country so far outside of China, with 41,035 cases as of Mar 19,
already had a death toll of 3,405 – surpassing the 3,248 deaths recorded in China.

“Many countries have exceeded the capacity to care for even mild cases in dedicated
health facilities, with many unable to respond to the enormous needs of the elderly,”
remarked Guterres during his Mar 19 UN’s address.1

Within the region of Southeast Asia, cases have soared as well – by mid-March,
numbers have crossed the triple-digit mark in at least five countries including
Malaysia, Thailand, Indonesia, the Philippines, and Singapore.

In Singapore, where the outbreak has largely been contained thus far, also saw a rise
in daily cases in March. More than two-thirds were imported cases involving mostly
residents or long-term pass holders returning from abroad.

“The health catastrophe makes clear that we are only as strong as the weakest
health system,” said Guterres. “Global solidarity is not only a moral imperative, it is in
everyone’s interests.”

“Urgent and aggressive measures are the need of the hour. We need to act now,”
implored Dr Poonam Khetrapal Singh, WHO Regional Director for Southeast Asia.2

17
DOCTOR| |MARCH
DOCTOR APRIL ISSUE
ISSUE
 COVER STORY
Stalling “Vici”
“When you realise that a public health emergency of
international concern was declared on January 30, and as
we speak, we are now mid-March, it’s very important to
understand that any country that still has not heeded the call
needs to be acting and acting fast: not least preparing the
population through appropriate risk communication,” said Dr
Gauden Galea, WHO Representative in China, during an
interview with the UN media.3
Several countries have come under fire for not acting
sooner, despite the unmistakable gravity of the situation.
By the time they came to grips with the reality, the virus had
already taken a foothold within their home ground. When
the healthcare system is overwhelmed, doctors would have
to triage which patients get to access the limited healthcare
resources – inevitably leaving some denied of a chance to
survive.
To avoid the healthcare system from collapsing, measures
for what epidemiologists called “flattening the curve” of the
pandemic need to be enacted, swiftly. The aim is to slow
down the spread of the virus such that large proportions of
the population are not ill at the same time.
Normally, a pandemic curve follows an exponential growth,
World on standstill
Italy, seeing its healthcare systems driven to the brink
by the blitz of the microscopic invader, became the first
country outside of China to impose a lockdown – initially
in the region of Lombardy, which then extended to other
northern provinces and later the entire nation.
The national quarantine serves to restrict movement of the
population, which hopefully, would slow down the spread
of the virus. Closure of all nonessential businesses was
mandatory.
As the daily new cases and death tolls continued to climb
globally, other countries followed suit in locking down their
cities/countries. So far, the UK, France, Spain, Belgium,
Germany, Denmark, Malaysia, New Zealand, Ireland, El
18
DOCTOR| |MARCH
DOCTOR
which would culminate at a high peak, and then decline
naturally when all susceptible individuals have been infected,
according to Galea. However, this did not happen in China.
Aggressive containment measures were taken to test,
trace, and isolate infected cases, and lockdown of an entire
city was ordered on the morning of Jan 23, when the total
confirmed cases in the country hit 571 with 17 dead as of the
previous day.
The country has since shown a downward trend in daily
number of new cases from its peak in mid-February.
“China has demonstrated that the course of the outbreak can
be altered,” Galea said. “One: the shape of the course of the
events … appears very unnatural. It is an epidemic that has
been nipped as it was growing and stopped in its tracks.”
“So, that’s a big lesson that the natural course of the
outbreak does not need to be a very high peak that
overwhelms health services. This lesson in containment,
therefore, is a lesson that other countries can learn from
and adapt for their own circumstances,” he stated during the
UN’s interview.
Salvador, and Peru have gone on nationwide lockdowns.
The US and the Philippines have imposed enhanced
community quarantine in certain regions and are mulling
over the expansion of quarantine zones.
“It appears that the strict measures China took may have
‘bought the world some time’ but did not prevent the global
dissemination of SARS-CoV-2,” commented experts
in JAMA’s opinion column. [JAMA 2020;doi:10.1001/
jama.2020.3072]
The question of how best to fight the war remains a
topic of debate, and varies depending on the phases of
outbreak, cultures, resources, governments, and laws
involved.
APRIL ISSUE
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 COVER STORY
Alternative strategies
Having kept the outbreak largely under control without
resorting to lockdowns so far, Singapore, Hong Kong, and
Japan held important lessons, according to a commentary
from ten experts led by Dr Helena Legido-Quigley of NUS**
Saw Swee Hock School of Public Health, Singapore.
[Lancet 2020;395:848-850]
These countries had focused on early detection,
quarantine, and treatment – principles of which constitute
the overarching theme of the recommendations by the
WHO, after a fact-finding mission in China.
To achieve these, the three countries had scaled up their
laboratory testing capacity, readjusted surveillance systems
to identify potential cases, and adapted financing measures
to shift all direct costs for treatment to the governments,
pointed out Legido-Quigley and co-authors.
“The first [lesson] is that integration of services in the health
system and across other sectors amplifies the ability to
absorb and adapt to shock,” they wrote.
“The second is that the spread of fake news and
misinformation constitutes a major unresolved challenge.
From containment to mitigation
Containment strategies such as quarantine work when the
number of infected patients is small and in concentrated
locales, according to Drs Stephen Parodi and Vincent Liu of
Kaiser Permanente, Oakland, California, US, in an opinion
paper. [JAMA 2020;doi:10.1001/jama.2020.3882]
However, they also noted that disease containment requires
significant healthcare resources such as isolation rooms,
personal protective equipment, and healthcare personnel.
“As COVID-19 spreads both in the US and around the world,
it may not be possible to care for all patients in this manner,”
wrote Parodi and Liu. “It is critically important that the
strategy for slowing the spread of the COVID-19 pandemic
change from containment to mitigation.”
Mitigation strategies aim to slow the further spread of
virus and reduce the demand for health care use. Social
*WHO: World Health Organization
**NUS: National University of Singapore
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
1
https://www.un.org/en/un-coronavirus-communications-team/above-all-human-crisis-calls-solidarity
2
https://www.who.int/southeastasia/news/detail/17-03-2020-who-calls-for-urgent-aggressive-actions-to-combat-covid-19-as-cases-soar-in-south-east-asia-region
3
https://news.un.org/en/story/2020/03/1059502
4
https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-mission-briefing-on-covid-19---13-march-2020
19
DOCTOR| |MARCH
DOCTOR
Finally, the trust of patients, healthcare professionals,
and society as a whole in government is of paramount
importance for meeting health crises,” the experts
continued.
“Timely, accurate, and transparent risk communication
is essential and challenging in emergencies because it
determines whether the public will trust authorities more
than rumours and misinformation,” they explained.
In Singapore, detailed clinical and logistics information is
disseminated to the public daily through mainstream media
and Whatsapp group. These platforms were also used to
debunk circulating misinformation.
In addition, there was also a stepwise series of entry
restrictions for visitors from China, which later extended
to those from France, Germany, Italy, Iran, Republic
of Korea, and Spain. In view of the rising imported
cases, no visitors are allowed to enter or transit
through Singapore starting Mar 23, while all returning
residents are served 14-day stay-home notice (except
those returning from Hubei province, who would be
quarantined).
distancing is one measure under the strategy, which can take
the forms of prohibition of large gatherings, staggered work
schedules, and distance learning for students, among others.
“[We] must take a comprehensive approach. Not testing
alone. Not contact tracing alone. Not quarantine alone. Not
social distancing alone. Do it all,” said WHO Director-General
Dr Tedros Adhanom Ghebreyesus during a recent WHO
media briefing on COVID-19.4
“We are in an unprecedented situation and the normal
rules no longer apply. We cannot resort to the usual tools
in such unusual times,” said Guterres. “The creativity of the
response must match the unique nature of the crisis – and
the magnitude of the response must match its scale.”
“This is, above all, a human crisis that calls for solidarity,” he
proclaimed.
APRIL ISSUE
ISSUE
 COVER STORY

How COVID-19
has changed our lives
ELVIRA MANZANO

T
13
he coronavirus has been spreading
at a frantic pace, isolating families
and snuffing out lives. As hunger and
be prevented by building a global warning
and response system for outbreaks, from
recruiting, training, and equipping health

ways emotional contagion grip the nations, the

hope of a containment also dims. No one
workers, development of new tools and
approaches, to efforts in preventing and

to fight
has seen this enemy coming – the world containing the outbreaks.” [N Engl J Med
has underestimated COVID-19. 2015;372:1381-1384]

In a span of weeks, COVID-19 has

crashed economies, challenging even Why not robots?
the most well-equipped healthcare
systems and disrupting lives on a scale Gates’ call to action resonated in the
no one has imagined. The effects were COVID-19 war. A helper droid called Moxi
catastrophic – indefinite travel bans, has been developed by robot maker,
shortage of supplies, massive job losses, Diligent Robotics, to help hospital doctors
and dwindling opportunities. and nurses in their daily hospital errands.
 Miniature robots were also deployed to

  Worldwide, more than 783,171 people had disinfect trains and stations in Hong Kong,


 contracted the virus and 37,743 had died and to relieve overworked healthcare
– many of them breathed their last alone workers in China.
 and were buried without funerals. US,

  Italy, and Spain cases had eclipsed those Robots cannot be infected by the virus and
of China. At press time, Singapore had hence, they can be used to access even
 

 reported three fatalities from the infection, the most vulnerable populations. With the

 Hong Kong had 4, Malaysia had 37, and critical shortage of doctors and nurses,


 the Philippines had 78. Indonesia had the and the chronic fatigue syndrome creeping
highest in Southeast Asia at 122. up on them, fielding robots in virus-laden
quarantine centres may soon be the new
COVID-19 also brought about social norm.
consequences and psychological
sufferings. It has changed how we think,
Wash hands frequently with
soap and water. and work, and communicate. Now we Virus stays on air,
recoil from shaking hands, feel safer with surfaces – even faeces
1 distance. And with it comes the realization
that nothing matters more than health. As corona virus spreads, so has people’s
fear of surfaces. The virus can live up to
Good hygiene 4 hours on copper, a day on cardboard,
can prevent
infection.
World unprepared and 3 days on plastic and stainless steel.
Also, it can live in the air for up to 3
Microsoft founder and philanthropist Bill hours. [N Engl J Med 2020;doi:10.1056/
Gates, in his post-Ebola essay in 2015, NEJMc2004973]
had predicted what was to come: “There
is a significant chance that a substantially There is also evidence that the virus is
more infectious epidemic will come along shed for longer in faecal matter. Viral
Practise social distancing as over the next 20 years ... the next one RNA is detectable in faecal samples of
a prophylactic move.
could be much worse. And the world is not patients and remained positive even after
2 prepared.” respiratory samples tested negative,
suggesting that viral gastrointestinal
Best practice There is a critical need to reinforce basic infection can last even after viral
requires two arms’ public health systems and invest in better clearance from the respiratory tract.
length or disease surveillance and laboratory testing [Gastroenterology 2020;doi.org/10.1053/j.
approximately 2m 2m
capacity, he wrote. “The catastrophe can gastro.2020.02.055]
two metres between
you and others.
20
DOCTOR | APRIL ISSUE
 COVER STORY
3

Hence, handwashing makes sense from Cough into

a hygienic perspective and protects sleeves, not to
individuals from obvious risks. “COVID-19 has the person
changed how we next to you.
think, and work, and
The worst & the best communicate …
And with it comes
The pandemic has brought out the worst Avoid hugs and
in people — from hoarders of toilet rolls the realization that
kisses.
to mall shoppers breaching stay-home nothing matters more
advisories. Some opportunists even than health.” 4
cashed in on the crisis by hawking on
phony cures or jacking up prices of basic
Also kiss goodbye
goods. to handshakes. 2m 2m

Nevertheless, it also brought out the best

in us – from experts looking for a cure to
doctors and nurses risking their lives at
the frontlines, and the unnamed faces and
heroes of the pandemic. The compassion, Cancel non-essential
travels.
as well as the generosity of spirit and
action seen and felt, is overpowering. 5
You may get
The ibuprofen furor stuck abroad
if you don’t.
Some viral texts have warned against
taking ibuprofen, claiming it could make
COVID-19 symptoms worse. But experts
refuted these as unfounded allegations.
Professor Michele Barry from the Stanford Stop going
University in Stanford, California, US to the movies.
said there was no data to back this up.
Professor Garret FitzGerald from the 6
University of Pennsylvania’s Perelman Catch your
School of Medicine in Philadelphia, favourite
Pennsylvania agreed, saying: “It’s films online
all anecdote, and fake news off the instead.
anecdotes.”

GSK, in its website, said ibuprofen when

used as labelled is safe to reduce fever
and provide pain relief, but people should
consult their doctors or health providers. 7
Even the WHO said it is not aware of any
negative effects of ibuprofen beyond the Cancel
usual known side effects that limit its use non-essential
in certain populations. “Based on currently family events.
available information, the WHO does not
recommend against the use of ibuprofen.”

Words have a great impact on how people

respond, so does the language experts Ride trains and buses during
use to describe what this unseen enemy is. off-peak hours.
Fake news spreads confusion and creates
chaos at a time when clarity is in short 8
supply – the least we could do is fact-
Your decision will
check. Don’t make an already bad situation ultimately affect
worse. the trajectory
of the outbreak.
21
DOCTOR | APRIL ISSUE
 COVER STORY
9
Order food
and groceries
Why are there fewer
COVID-19 cases in children?
online to
minimize contact
with others.
STEPHEN PADILLA
T
he assumption that children are
less vulnerable to the coronavirus
10 disease 2019 (COVID-19) compared
to adults is not quite true and may even be
Stay home and dangerous, suggests a recent study.
avoid visitors.
COVID-19, which is caused by infection
with the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), appears to
virtually spare children, while those infected
tend to have less disease severity.
11 This seems to be the case either because
children are less frequently exposed
Opt for to the main sources of transmission or
teleconferencing they are less exposed to animals, said
instead of
Petra Zimmermann and Nigel Curtis
face-to-face
meetings. from the Department of Paediatrics,
Fribourg Hospital HFR, Switzerland.
[Pediatr Infect Dis J 2020;doi:10.1097/
INF.0000000000002660]
On the other hand, it is also possible that
children are more frequently asymptomatic
12 or have less severe symptoms and hence
Consult less often tested for COVID-19. This can
your doctor potentially result in underestimation of the
if you’re true numbers infected, according to the
unwell. authors.
A recent study by Bi Q. and colleagues in
Shenzhen, China, provided preliminary
evidence suggesting that the risk of
SARS-CoV-2 infection among children is
13
similar to that of the general population,
If returning from overseas, practise but the former are less likely to show
self-quarantine. Self-isolate if you have
any signs or develop severe symptoms.
symptoms: sore throat, fatigue, chills,
stuffy nose, poor appetite, muscle aches, [medRxiv;oi:10.1101/2020.03.03.20028423]
vomiting, diarrhoea, fever,
and cough. “However, the importance of children in
transmitting the virus remains uncertain,”
Zimmermann and Curtis stated in their review.
CoVs (eg, SARS-CoV, SARS-CoV-2, and
Middle East Respiratory Syndrome [MERS]-
CoV) cause respiratory and gastrointestinal
symptoms in humans, with clinical signs
ranging from a common cold to a more
severe disease, including bronchitis,
pneumonia, severe acute respiratory
distress syndrome, multi-organ failure, or
death.
22
DOCTOR | APRIL ISSUE
“The clinical, laboratory, and radiologic
features in children are similar for all novel
CoVs, except more children infected with
SARS-CoV presented with fever compared
with SARS-CoV-2 or MERS-CoV,” the
authors said.
Thus far, no deaths have been reported in
children for SARS-CoV or SARS-CoV-2,
with the exception of infants of mothers who
were infected during pregnancy in the case
of the former, they added.
There is currently no cure for COVID-19
available, and the trial for an investigational
vaccine is ongoing. However, a study
published by the Zhejiang University School
of Medicine suggests the use of nebulized
interferon alpha-2b and oral lopinavir/ritonavir
together with corticosteroids for complications
and intravenous immunoglobulin in children
with severe cases. [World J Pediatr
2020;doi:10.1007/s12519-020-00345-5]
The authors stressed that none of these
therapies have shown a “clear benefit”
in the treatment of other novel CoVs, so
whether they will be effective against SARS-
CoV-2 remains questionable. In addition,
neither the World Health Organization nor
the US Centers for Disease Control and
Prevention endorses any specific therapy
in children or adults. [https://apps.who.int/
iris/handle/10665/330893; https://www.cdc.
gov/ coronavirus/2019-ncov/hcp/clinical-
guidance-management-patients.html]
“Needless to say, strict hand hygiene needs
to be applied and visitors should be avoided
or limited to an absolute minimum,” the
authors said.
SARS-CoV-2, the virus responsible for
COVID-19, was first detected in Wuhan,
China, in 2019 and quickly spread across
the globe as reports of the discovery of the
novel coronavirus were allegedly blocked
at first and a travel ban to and from the city
was not immediately imposed. COVID-19
cases worldwide are nearing the 200,000
mark, with more than 7,800 deaths, as of 18
March 2020.

COVID-19 not a ‘bioweapon’
manufactured in lab
TRISTAN MANALAC
T
here is no evidence to support
the claims that severe acute
respiratory disease coronavirus
2 (SARS-CoV-2), the causative agent
behind the 2019 novel coronavirus disease
(COVID-19), is a laboratory construct and
purposefully manipulated, a new study
suggests.
“It is improbable that SARS-CoV-2
emerged through laboratory manipulation
of a related SARS-CoV-like coronavirus,”
the authors asserted. [Nat Med
2020;doi:10.1038/s41591-020-0820-9]
Drawing from the published descriptions
of the SARS-CoV-2 genome, the authors
identified two notable features of the virus.
The first is a receptor-binding domain
(RBD) located on the SARS-CoV-2 spike
protein, which carries a six-amino acid
signature that determines its binding
affinity. [J Virol 2020;doi:10.1128/
JVI.00127-20]
Based on structural and biochemical
studies, this domain makes SARS-CoV-2
optimized to latch on to the ACE2* protein
of many different species, including ferrets,
cats, and humans. [J Virol 2020;doi:
10.1128/JVI.00127-20; bioRxiv 2020;doi:
10.1101/2020.02.19.956581; Science
2020;doi:10.1126/science.abb2507]
Despite this, computational studies have
determined that the interaction between
the SARS-CoV-2 RBD and the human
ACE2 receptor protein remains unideal.
Moreover, the amino acid sequence
in this particular virus diverges from
signatures previously identified to allow
optimal binding. [J Virol 2020;doi:10.1128/
JVI.00127-20; J Virol 2008;82:2274-2285]
“Thus, the high-affinity binding of the
SARS-CoV-2 spike protein to human ACE2
is most likely the result of natural selection
on a human or human-like ACE2 that
permits another optimal binding solution
to arise,” the authors said. “This is strong
evidence that SARS-CoV-2 is not the
product of purposeful manipulation.”
COVER STORY
The second notable feature of SARS-
CoV-2 is a functional polybasic cleavage
site, located in the boundary between its
two subunits. Though its exact function
and implications on transmissibility and
pathogenicity remain unknown, this
cleavage site does offer additional evidence
against claims of purposeful manipulation,
the authors noted.
Coronaviruses resembling SARS-CoV exist
in cell cultures in biosafety level 2 labs all
over the world. However, the likelihood of
acquiring such a polybasic cleavage site via
culture passage is low.
“New polybasic cleavage sites have been
observed only after prolonged passage
of low-pathogenicity avian influenza
virus in vitro or in vivo,” the authors said.
“Furthermore, a hypothetical generation
of SARS-CoV-2 by cell culture or animal
passage would have required prior isolation
of a progenitor virus with very high genetic
similarity, which has not been described.” [J
Virol 2001;75:4439-4443]
Hypothetically, even if this SARS-CoV-2 had
been produced in the lab, it would need to
undergo several rounds of passage in cell
cultures of animals with ACE2 receptors
resembling that of humans. This has not yet
been described in the literature, the authors
added.
23
DOCTOR | APRIL ISSUE
Instead, they postulate that SARS-CoV-2
had come to be through two possible
mechanisms: natural selection in animal
reservoirs, before zoonosis, or in humans,
after zoonotic transfer. It is important to
resolve this question to better prepare for
similar outbreaks in the future, the authors
said.
If, for instance, SARS-CoV-2 had acquired
its key mutations after the transfer to
humans, then an outbreak event of a similar
global scale is unlikely to repeat itself even
after several zoonotic transfers. But if the
virus had been incubated and mutated
inside an animal host, the risk of future re-
emergence will remain high.
“Obtaining related viral sequences
from animal sources would be the most
definitive way of revealing viral origins. The
identification of a potential intermediate host
of SARS-CoV-2, as well as sequencing of the
virus from very early cases, would similarly
be highly informative,” the authors said.
“Irrespective of the exact mechanisms by
which SARS-CoV-2 originated via natural
selection, the ongoing surveillance of
pneumonia in humans and other animals is
clearly of utmost importance,” they added.
*Angiotensin-converting enzyme 2, the protein
identified as the functional receptor for SARS-CoV-2

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Carotid surgery outperforms stenting
in patients 75+ years
ELVIRA MANZANO
P
atients aged ≥75 years are at a
higher likelihood of having poor
outcomes after carotid artery
stenting (CAS) than carotid endarterec-
tomy (CEA), according to a combined
analysis of two studies with over 2,500
patients.
CAS expands the carotid artery
through insertion of a stent whereas
CEA is a surgical procedure to remove
plaque deposits in the carotid artery and
increase blood flow to the brain. More re-
cently, CAS has emerged as an alterna-
tive to CEA in patients with cerebral large
artery disease. Age has been shown to
be an effect modifier for CAS with older
patients at a higher risk, but not for CEA.
The analysis included data from
2,544 elderly asymptomatic patients from
CREST* (n=1,091) and ACT I (n=1,453)
trials with ≥70 percent carotid stenosis
and treated with CAS or CEA, on top of
standard management for cardiovascu-
lar risk factors. Patients from CREST had
no age ceiling; those from ACT 1 were 79
years or younger. [ISC 2020, abstract 70]
The prespecified primary outcome
was the combined incidence of peripro-
cedural stroke, myocardial infarction [MI],
or death, or any incidence of ipsilateral
stroke within 4 years after randomization.
Among patients who underwent CAS,
the incidence of the primary outcome
was 30 percent higher among patients
aged 65–74 years vs patients aged <65
years, but the difference was not statisti-
cally significant.
However, patients aged 75+ years
were at a substantially higher risk (hazard
ratio [HR], 2.9; p=0.001). By contrast,
the risk did not differ by age in patients
who underwent CEA.
CONFERENCE COVERAGE
Largest data set for CAS,
CEA
The risk for poor outcomes in patients
who underwent CAS “abruptly increased
around age 75” vs patients who under-
went CEA, and these results mirrored the
findings from a similar combined analysis
of data from four major randomized trials
that compared CEA and CAS in patients
with symptomatic carotid disease, said
study author Dr Jenifer Voeks, a neurolo-
gy researcher at the Medical University of
South Carolina in Charleston, South Car-
olina, US. She added their analysis has
the largest dataset thus far to compare
CAS and CEA by age in asymptomatic
patients.
Which patient would benefit
from CAS?
“CAS appears to be a reasonable alter-
native to CEA in patients ≤70 years, but
in those aged 70 years, and certainly
in those above age 75, age-related risk
factors such as cerebrovascular anat-
omy and underlying cerebral pathology
should be carefully considered before
selecting patients for CAS,” Voeks said.
24
DOCTOR | APRIL ISSUE
Commenting on the findings, Dr Mai
Nguyen-Huynh, a vascular neurologist
from Kaiser Permanente Northern Cali-
fornia in Oakland, California, US, said it’s
not surprising that CEA did better than
CAS in the analysis. There is already evi-
dence that CAS does not perform as well
as CEA in older patients with symptom-
atic carotid artery disease, likely because
older patients have more fragile and
torturous blood vessels that make CAS
more challenging and raise the potential
for more adverse events, she said.
As more and more experts have been
turning to new drugs as a treatment op-
tion for patients with advanced athero-
sclerotic carotid artery disease, this has
turned into a state of “equipoise” for
pharmacological vs interventional man-
agement, she added. CREST 2** would
attempt to compare CEA and CAS with
medical management, and results are
expected in 2021.
* CREST: Carotid Revascularization Endarterectomy
Versus Stenting Trial
** CREST 2: Carotid Revascularization and Medical
Management for Asymptomatic Carotid Stenosis
Trial

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
TST 5-year data:
LDL <70 cuts risk
of recurrent stroke
PEARL TOH
T
reating stroke patients to a target
LDL cholesterol (LDL-C) of <70
mg/dL significantly reduced the
risk of recurrent stroke and other major
cardiovascular (CV) events, without rais-
ing the risk of intracranial haemorrhage
(ICH), a subanalysis of the French cohort
in the TST* trial has shown.
“Current AHA/ASA** guidelines rec-
ommend ‘intense’ statin therapy after an
ischaemic stroke of atherosclerotic origin
but does not stipulate a target level of
LDL-C,” said Professor Pierre Amaren-
co of Bichat University Hospital, Paris,
France during the ISC 2020 Meeting.
“Therefore, there was uncertainty about
the target level of LDL-C appropriate to
reduce CV events after stroke.”
Analysing the French cohort of the
TST trial with a median follow-up of 5.3
years, the investigators found that the pri-
mary composite outcome occurred less
frequently in patients treated to an LDL-C
target of <70 mg/dL vs 100±10 mg/dL
(9.6 percent vs 12.9 percent; hazard ratio
[HR], 0.74; p=0.019). [ISC 2020, ab-
stract LB 19; Stroke 2020;doi:10.1161/
STROKEAHA.119.028718]
“The positive result of the TST trial,
with a number needed to treat of 30, sets
a new target range for LDL-C to achieve
<70 mg/dL during 5 years after a stroke
of atherosclerotic origin,” said Amarenco.
He also pointed out that the result
was obtained while other risk factors
were controlled at optimal levels as well,
such as blood pressure (mean 135/75
CONFERENCE COVERAGE
mm Hg), HbA1c <7 percent, and active
smoking status, which reduced from 30
percent at baseline to 5 percent over the
course of the study.
The finding was consistent with that
in the overall population, which included
2,148 French and 742 Korean partici-
pants. The primary composite outcome
was also reduced with more intensive vs
less intensive LDL-C lowering (rates of
primary outcome, 8.5 percent vs 10.9
percent; HR, 0.78; p=0.04), which has
been reported previously.
The current subanalysis focused only
on the French cohort as it was larger with
a longer median follow-up of 5.3 years,
compared with 2.0 years in the Korean
patients. The longer follow-up was also
comparable to the SPARCL*** trial (4.9
years median follow-up), on which the
guideline recommendation for an intense
LDL-lowering therapy after an ischaemic
stroke was based on.
Participants in the subanalysis were
2,148 French patients (mean 67 years,
~68 percent male) with ischaemic stroke
of atherosclerotic origin, who were ran-
domized 1:1 to a target LDL-C level of
<70 mg/dL vs 100±10 mg/dL. The pri-
mary composite outcome comprised
ischaemic stroke, myocardial infarction
(MI), new symptoms (such as unstable
angina requiring hospitalization or TIA#)
requiring urgent coronary or carotid re-
vascularization, and vascular death.
On average, the LDL-C levels
achieved were 66 mg/dL for the more
aggressive target and 96 mg/dL for the
less aggressive target.
25
DOCTOR | APRIL ISSUE
The composite of primary outcome
and ICH was similarly reduced by 25
percent (p=0.021), as was cerebral in-
farction or ICH (all strokes; reduction, 28
percent; p=0.023).
“Targeting an LDL-C of <70 mg/dL
during 5.3 years avoided one subse-
quent major vascular event in four pa-
tients, as well as one ischaemic stroke
or ICH in four patients, without increas-
ing the risk of ICH … as compared with
a target LDL-C of 100 mg/dL,” report-
ed Amarenco. ICH was reported in 13
and 11 patients, respectively (HR, 1.17;
p=0.70).
He also believed that further reduc-
tion in LDL-C may provide further benefit,
without any lower threshold, as suggest-
ed by previous studies included in the
CTT## meta-analysis.
“These studies and our trial results
suggest that lowering LDL-C with new,
more potent, lipid lowering drug in fu-
ture randomized clinical trial may further
address the residual risk in patients with
stroke,” the investigators said.
“[But for now, physicians] may find
useful in practice to target a number,
such as <70 mg/dL as a first objective in
prevention of new stroke, as suggested
by our results,” they stated.
* TST: Treat Stroke to Target
** AHA/ASA: American Heart Association/American
Stroke Association
*** SPARCL: Stroke Prevention by Aggressive
Reduction in Cholesterol Level
# TIA: Transient ischaemic attack
## CTT: Cholesterol Treatment Trialists

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Low SHBG levels
may predict
stroke risk in
postmenopausal
women
ELAINE SOLIVEN
L
ow levels of sex hormone-binding
globulin (SHBG) may be associated
with a higher risk of incident isch-
aemic stroke in postmenopausal wom-
en, according to a study presented at
ISC 2020.
“SHBG [is] a protein that binds to
and regulates available testosterone and
oestradiol,” said the researchers. “In this
prospective cohort of postmenopausal
women, there was a significant inverse
association between SHBG levels and
ischaemic stroke risk, suggesting that
SHBG could improve risk stratification
for predicting ischaemic stroke in post-
menopausal women.”
Using data from the Women’s Health
Initiative database between 1993 and
1998, the researchers identified 13,192
postmenopausal women (aged 63–67
years) included in ancillary studies who
had serum SHBG measurements and
no history of stroke at baseline. Partic-
ipants were assessed by SHBG quin-
tiles (Q1 as the lowest [median SHBG
CONFERENCE COVERAGE
23.3] and Q5 as the highest [median
SHBG 107]). [ISC 2020, abstract 73;
Stroke 2020;doi:10.1161/STROKEA-
HA.120.028905]
During a mean follow-up of 11.6
years, a total of 768 ischaemic stroke
events were reported.
Women with a low SHBG level had
a significantly higher risk of stroke than
those with a high SHBG level (adjusted
hazard ratio [HR]*, 1.61, 95 percent con-
fidence interval [CI], 1.19–2.19; p=0.04).
In an exploratory analysis of potential
mediators, including diabetes (HR, 1.63,
95 percent CI, 1.26–2.12; p=0.01) and
total oestradiol (HR, 1.99, 95 percent CI,
1.49–2.66; p<0.0001) in the models, the
relationship between the incident isch-
aemic stroke and low SHBG attenuat-
ed, “but did not eliminate the significant
inverse associations,” the researchers
noted.
“Though these findings are novel
with respect to the evaluation of stroke
as the primary outcome, our findings are
26
DOCTOR | APRIL ISSUE
supported by [previous] studies show-
ing an inverse association between
SHBG and cardiovascular disease,”
the researchers said. [Circulation
2003;108:1688-1693]
“Our findings of the association be-
tween low SHBG and stroke risk have
potential implications for the way in which
we [can] predict stroke risk in postmeno-
pausal women … suggesting that a
measure of endogenous sex hormones
like SHBG could possibly improve the
performance of commonly used predic-
tion tools.”
“Future research is needed on the
nature of the relationship between SHBG
and stroke (causal or not), the poten-
tial mechanisms, and the ability to use
SHBG to improve our current methods
of stroke prediction and prevention in
women,” they added.
*adjusted for age, race/ethnicity,
SHBG assay, body mass index, history
of hypertension, alcohol use, smoking
status, physical activity, and reproductive
factors.

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Apixaban outperforms warfarin
regardless of prior stroke, TIA, or TE
ELVIRA MANZANO
A
pixaban outperformed warfarin in
preventing ischaemic events re-
gardless of prior stroke, transient
ischaemic attack (TIA), or thromboem-
bolic event (TE) in patients with atrial
fibrillation (AF) with recent acute coro-
nary syndrome (ACS) or percutaneous
coronary intervention (PCI), a prespec-
ified secondary analysis of the AUGUS-
TUS trial has shown.
“These results
are reassuring for
physicians … ”
Bleeding was lower with the apix-
aban-containing regimen than with war-
farin, so was the rate of death or rehos-
pitalization. In both arms, the addition of
aspirin resulted in greater bleeding with
no difference in efficacy. [ISC 2020, ab-
stract LB22]
“A strategy of apixaban plus a P2Y12
inhibitor without aspirin has the most
favourable outcomes, and triple thera-
py — a vitamin K antagonist [VKA] plus
aspirin plus a P2Y12 inhibitor — should
be avoided,” said lead investigator Dr
Maria Cecilia Bahit, chief of cardiolo-
AHA photo
Dr Maria Cecilia Bahit
CONFERENCE COVERAGE
gy at INECO Neurociencias in Rosario,
Santa Fe, Argentina. “These results are
reassuring for physicians … even in a
high-risk group with prior stroke, ‘less is
more’.”
Results support AUGUSTUS
The new analysis supports the main
findings of the AUGUSTUS trial which
demonstrated less bleeding and fewer
deaths and hospitalizations with an an-
tithrombotic regimen that included apix-
aban without aspirin vs treatment with
a VKA (warfarin) plus aspirin in patients
with AF, with either ACS or PCI and re-
ceiving a P2Y12 inhibitor (clopidogrel in
over 90 percent of patients). [N Engl J
Med 2019; 380:1509-1524]
AUGUSTUS included 4,614 pa-
tients. The sub-analysis divided the AU-
GUSTUS population into two groups:
patients with prior stroke, TIA, or TE and
those without. Of the 4,581 patients
with information available about prior
stroke, 13.8 percent had prior stroke,
TIA, or TE. They were also older, with
higher CHA2DS2-VASc and HAS-BLED*
scores, and were more likely to have
prior bleeding, heart failure, diabetes,
and previous use of oral anticoagulant.
“In both groups, apixaban was safer
than warfarin, causing less major bleed-
ing and resulting in less death or hospi-
talization regardless of prior stroke, TIA,
or TE,” Bahit reported at ISC 2020. “Pa-
tients without prior stroke, TIA, or TE re-
ceiving aspirin had higher bleeding rates
than those not on aspirin, whereas the
difference between aspirin and placebo
appeared to be less substantial in those
with prior stroke, TIA, or TE.”
Commenting on the study, Dr Mitch-
ell S.V. Elkind, president-elect, Amer-
ican Heart Association and professor
of neurology and epidemiology at Co-
27
DOCTOR | APRIL ISSUE
lumbia University New York, New York
City, New York, US said: “The AUGUS-
TUS trial was a study that looked at a
complicated group of patients. These
patients often require anticoagulation for
AF and antiplatelet agents for coronary
intervention, heart attack, and perhaps,
displaced coronary artery. And so, the
question has always been: How many
blood thinners should these patients be
on? Potentially, they could be on three
different agents [an anticoagulant and
two antiplatelet drugs], and we know
that all of those drugs together pretty
dramatically increase the risk of bleed-
ing.”
Can we do without aspirin?
The results seen in the AUGUSTUS trial
held true for those with a history of cere-
brovascular disease in the secondary
analysis. “Apixaban was more effective
than warfarin, with a lower risk of bleed-
ing in those with a history of cerebro-
vascular disease, just as it was in those
without,” Elkind added.
“Overall, the results confirmed that
the use of apixaban appeared safer and
these patients need not be on aspirin
as well as other antiplatelet regimen.
Patients with a history of stroke had a
lower risk of bleeding … and so, one
could argue that they should be on an
agent like apixaban, as well as an alter-
nate antiplatelet agent, like clopidogrel,
for example, without the addition of as-
pirin.”
* scoring systems used to estimate stroke and
bleeding risk, respectively

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Robot used to treat brain aneurysm
for the first time
ELVIRA MANZANO
F
or the first time, surgeons have suc-
cessfully used a robot to treat brain
aneurysm, a study presented at ISC
2020 has shown. This would eventually
allow for remote robotic surgery in pa-
tients with limited or no access to endo-
vascular treatments currently.
“This is very exciting – to have robot-
ic endovascular treatments available,”
commented Dr Mitchell S.V. Elkind,
president-elect of the American Heart
Association and professor of neurology
and epidemiology at Columbia University
in New York City, New York, US, but is
not part of the study. “It’s early yet, we
don’t know exactly where this is gonna
go. Robotic therapy and minimally inva-
sive procedures have been around, of
course, in general surgery and cardiotho-
racic surgery, but [these are] not applied
yet as much to endovascular treatments,
treatments for stroke, and vascular mal-
formations ... So, this is very exciting to
have a tool available to treat these pa-
tients remotely.”
Researchers in Toronto, Canada pre-
sented a case of a 64-year-old female
patient who presented to their institution
with an unruptured basilar aneurysm the
size of 10mm. Endovascular intervention
using the CorPath GRX robotic system
AHA photo
Dr Vitor Mendes Pereira
CONFERENCE COVERAGE
was performed on the patient. A guide
catheter was placed in the right vertebral
artery, and an intermediate catheter ad-
vanced to the V4 segment. A microca-
theter was then connected to the robotic
drive by a robotic technologist, with the
presence of two neurointerventionalists,
one of whom operated the robot from
the control terminal. The same microca-
theter was used to enter the aneurysm
sac. Stent-assisted coiling of the aneu-
rysm was done using the robot. [ISC
2020, abstract LB23]
“Our experience is the first step to-
wards achieving our vision of remote
neurovascular procedures,” said lead
author Dr Vitor Mendes Pereira, a neu-
rosurgeon and neuroradiologist at the
Toronto Western Hospital and professor
of medical imaging and surgery at the
University of Toronto, both in Toronto,
Canada. “The ability to robotically per-
form intracranial aneurysm treatment is a
major step forward in neuro-endovascu-
lar intervention.”
Since the first case, his team has
successfully performed five additional
aneurysm treatments using the robot,
28
DOCTOR | APRIL ISSUE
which included deploying flow-diverting
stents.
“The expectation is that future robot-
ic systems will be able to be controlled
remotely. One day, I could be at my hos-
pital and deliver therapy to a patient hun-
dreds or even thousands of kilometres
away,” said Mendes Pereira. “The ability
to deliver rapid care through remote ro-
botics for time-critical procedures such
as stroke could have a huge impact on
improving patient outcomes and allow us
to deliver cutting-edge care to patients
everywhere, regardless of geography.”
Elkind couldn’t be more excited. “It’s
really like science fiction stuff. It sounds
really exciting and it has great potential.
One wonders whether there really will be
an opportunity to have the tools them-
selves at the smaller centres where this
might be performed … we’ll have to see
how this develops.”
More work will have to be done, he
said. But this is a first step in a very ex-
citing direction.
* comprising Crohn’s disease and ulcerative colitis
 CONFERENCE COVERAGE
International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US

Gum disease tied to stroke risk

AUDREY ABELLA

T
wo studies presented at ISC 2020
reflected the association between
gum or periodontal disease and
a higher risk of stroke, underscoring the
potential role of gum treatment for stroke
prevention.

“[I]nflammation appears to play a

major role in the development and wors-
ening of atherosclerosis or ‘hardening’
of blood vessels. [Therefore,] we inves-
tigated if gum disease is associated with
blockages in brain vessels and strokes
caused by atherosclerosis of the brain
vessels,” said Dr Souvik Sen from the
University of South Carolina School of
Medicine in Columbia, South Carolina,
US, who authored both studies.

(adjusted OR [adjOR], 3.1, 95 percent 2.1, 95 percent CI, 1.2–3.8; p=0.015),

“Future studies are
needed to determine
if treatment of
gingivitis can prevent
the development and
progression of ICAS [and
consequently reduce]
the risk of stroke”
In a cross-sectional study, 265 con-
secutive patients (mean age 64 years, 56
percent male, 33 percent with periodon-
tal disease) who have had a stroke (20
percent caused by large-artery athero-
thrombosis) were evaluated. [ISC 2020,
abstract 85]
The incidence of stroke due to pos-
terior circulation disease was threefold
higher among individuals with vs with-
out periodontal disease (12 percent vs 5
percent; crude odds ratio [cOR], 3.0, 95
percent confidence interval [CI], 1.1–7.9;
p=0.03). This association was sustained
after adjusting for confounding factors*
CI, 1.04–9.1; p=0.004).
Moreover, a significantly higher risk of
stroke due to intracranial atherosclerosis
(ICAS) was observed among participants
with vs without periodontal disease (20
percent vs 8 percent; cOR, 2.6, 95 per-
cent CI, 1.3–5.6; p=0.01), which persist-
ed after adjusting for the same covari-
ates (adjOR, 2.6, 95 percent CI, 1.1–5.8;
p=0.004).
No stroke history
In another study, researchers evaluat-
ed the presence of intracranial arterial
blockage in 1,145 individuals (mean age
76 years, 55 percent female) from the
DARIC** study who had not experienced
a stroke. Of these, 10 percent had ≥50
percent ICAS, suggesting severe arterial
blockage, while the remaining 90 percent
had 0–50 percent ICAS. [ISC 2020, ab-
stract 136]
The odds of having ≥50 percent
ICAS were substantially higher among
subjects with vs without gingivitis (cOR,
which was sustained even after adjust-
ing for confounding variables*** (adjOR,
2.4, 95 percent CI, 1.3–4.5; p=0.006).
These suggest that individuals with in-
flamed gums had twice the risk of having
moderate-to-severe arterial narrowing
in the brain due to plaque buildup, thus
increasing the likelihood of developing a
stroke, noted Sen.
Although both studies did not eval-
uate causality, the findings highlight the
importance of identifying gum disease
as a potential underlying factor in stroke
development and/or progression. “It is
important for clinicians to … address
gum disease … [G]ingivitis is reversible.
[Therefore,] future studies are needed to
determine if treatment of gingivitis can
prevent the development and progres-
sion of ICAS [and consequently reduce]
the risk of stroke,” said Sen.
* age, race, hypertension, hyperlipidaemia, coronary
artery disease, atrial fibrillation, diabetes, HbA1c,
and smoking status
** DARIC: Dental Atherosclerosis Risk in Communities
*** age, hype­rtension, and LDL cholesterol

29
DOCTOR | APRIL ISSUE

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Golfing regularly
may help older
adults live longer
STEPHEN PADILLA
P
laying golf at least once a month
can lower the risk of death
among elderly persons, accord-
ing to a study presented at ISC 2020.
However, the protective effect of
golfing does not extend to a reduction
in cardiovascular events.
“Our study is perhaps the first of its
kind to evaluate the long-term health
benefits of golf, particularly one of the
most popular sports among older peo-
ple in many countries,” said lead au-
thor Dr Adnan Qureshi and executive
director of the Zeenat Qureshi Stroke
Institutes and professor of neurology at
the University of Missouri in Columbia,
Missouri, US in a statement.
Qureshi and colleagues analysed
data from the Cardiovascular Health
Study, a prospective observational
cohort study of risk factors for cardio-
vascular disease in adults aged ≥65
years. Participants underwent annual
extensive clinical examinations and six
monthly clinic visits from 1989 through
1999. Once clinic visits ended, they
were contacted by phone to determine
the occurrence of any cardiovascular
event. [ISC 2020, abstract TP172]
CONFERENCE COVERAGE
The researchers inquired about the
participants’ golf status at baseline and
conducted longitudinal follow-up for a
mean of 13 years. Regular golf players
referred to those who played golf at least
once a month. Cox proportional hazards
analysis was performed to ascertain the
effect of playing golf on incident myo-
cardial infarction (MI), stroke, and death
during follow-up after adjusting for con-
founders.
“Our study is perhaps
the first of its kind to
evaluate the long-term
health benefits of golf”
A total of 5,888 participants (mean
age 72.8 years, 41.9 percent men)
were identified, of which 384 individuals
played golf regularly. Thirty-one (8.1 per-
cent) regular golfers had a stroke and 38
(9.9 percent) had MI during follow-up.
Overall mortality rate stood at 1,115
death per 100,000 population. The rate
of death was significantly lower among
individuals who played golf regularly than
those who did not (15.1 percent vs 24.6
percent, respectively). No difference was
noted in the rates of MI or stroke among
those who played golf regularly.
30
DOCTOR | APRIL ISSUE
After adjusting for age, race, gender,
hypertension, and diabetes, multivari-
able analysis revealed that individuals
who played golf regularly had a lower
risk of death (hazard ratio [HR], 0.6, 95
percent confidence interval [CI], 0.4–0.7;
p<0.0001) compared with those who did
not.
On the other hand, the risk of MI (HR,
1.0, 95 percent CI, 0.7–1.3) or stroke
(HR, 1.0, 95 percent CI, 0.7–1.5) was not
lower among regular golf players.
“While walking and low-intensity jog-
ging may be comparable exercise, they
lack the competitive excitement of golf,”
Qureshi said in a statement. “Regular ex-
ercise, exposure to a less polluted envi-
ronment, and social interactions provid-
ed by golf are all positive for health.”
In addition, adults can continue play-
ing golf until old age unlike other more
strenuous sports such as football, bas-
ketball, and tennis, among others. Stress
relief and relaxation are other benefits of
golfing that other sports do not offer.
In the US, golf is played by about 25
million people. Playing golf has been as-
sociated with a reduced risk of cardio-
vascular disease by providing regular ex-
ercise and stress relief, according to the
researchers.

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
ROSHINI CLAIRE ANTHONY
A
dding cilostazol to other antiplate-
let agents could potentially reduce
in-stent restenosis (ISR) among
patients with carotid artery stenosis who
undergo carotid artery stenting (CAS),
according to results of the CAS-CARE*
trial presented at ISC 2020.
The study population comprised 631
patients (mean age 69.8 years, 88.4 per-
cent male) with symptomatic (≥50 percent
stenosis) or asymptomatic (≥80 percent
stenosis) carotid artery stenosis who were
scheduled to undergo CAS within the
next 30 days. They had been randomized
to receive either cilostazol (100 or 200 mg
BID; n=325) plus other antiplatelet agents
or other antiplatelet agents only (n=306),
initiated 3 days pre-CAS and continued
for up to 2 years. A major proportion of
patients assigned to the cilostazol group
also received concomitant antiplatelet
agents (66.2, 60.3, and 6.4 percent also
received aspirin, clopidogrel, and other
antiplatelets, respectively).
Within 2 years post-CAS, ultrasound
diagnosed ISR incidence (≥50 percent)
was lower, though not statistically so,
among patients who received cilostazol
compared with those who received other
antiplatelet agents (9.5 percent vs 15.0
percent; p=0.039; hazard ratio [HR],
0.64, 95 percent confidence interval [CI],
CONFERENCE COVERAGE
Adding cilostazol to
other antiplatelet agents
could reduce post-CAS
restenosis risk
0.41–1.02; p=0.056). [ISC 2020, ab-
stract LB21]
Landmark analysis showed that the
benefit with cilostazol vs other agents
only occurred beyond 30 days of treat-
ment (10.3 percent vs 19.3 percent;
HR, 0.62, 95 percent CI, 0.39–0.98;
p=0.040), with no between-group differ-
ence in the first 30 days (0.6 percent vs
0.3 percent; HR, 1.89; p=0.598).
“[The researchers] did find that there
was some benefit to adding cilostazol,
and this is perhaps an exciting result
with the degree of restenosis dropping
from about 15 percent to about 9 per-
cent or so. However, the results were not
statistically significant,” noted Professor
Mitchell Elkind from Columbia Univer-
sity New York City, New York, US, and
president-elect of the American Heart
Association, who was not affiliated with
the study.
There was no significant difference
between cilostazol and other antiplate-
let agents in terms of a composite of CV
events** or all-cause death (HR, 0.95,
95 percent CI, 0.51–1.80; p=0.886),
or bleeding events (intracranial haem-
orrhage or systemic bleeding requiring
transfusion; HR, 1.66, 95 percent CI,
0.48–5.66; p=0.416).
Severe ISR (≥70 percent) also oc-
31
DOCTOR | APRIL ISSUE
curred at a similar rate between those
who received cilostazol or other antiplate-
let agents (HR, 0.50; p=0.108), as did
ischaemic (HR, 1.31; p=0.560) or haem-
orrhagic stroke (HR, 1.26; p=0.762).
“This is the first trial to show potential
effectiveness of medical management
for the prevention of ISR after CAS,” said
lead author Dr Hiroshi Yamagami from
the National Hospital Organization Osaka
National Hospital, Japan.
However, he noted that the all-Jap-
anese study population prevents the
results from being extrapolated to other
populations.
“[CAS] is being done frequently now
for patients with both symptomatic and
asymptomatic carotid stenosis, and it’s
still not clear what the best way is to pre-
vent the vessel from re-stenosing,” said
Elkind. “These results may prompt fur-
ther study in this area.”
While these findings are “a great thing
to have available in the armamentarium,”
they cannot be applied to routine use in
patients with stents, he added.
* CAS-CARE: Carotid Artery Stenting with Cilostazol
Addition for Restenosis
** composite of stroke, transient ischaemic attack
(TIA), myocardial infarction (MI), aortic dissection,
aortic rupture, pulmonary embolism, peripheral
artery disease

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
tPA before mechanical thrombectomy:
To skip or not?
ELAINE SOLIVEN
S
kipping intravenous (IV) tissue
plasminogen activator (tPA) be-
fore mechanical thrombectomy
(MT) may have similarly favourable out-
comes to using tPA pre-MT in patients
with acute stroke, according to the SKIP*
study presented at ISC 2020.
“Both IV tPA and MT have [proven]
evidence for benefits in ischaemic stroke
patients, … [but] we really don’t know
whether [skipping] IV [tPA] before MT is
indeed for LVO** patients,” said Dr Ken-
taro Suzuki from the Department of Neu-
rology at Nippon Medical School Hospi-
tal in Tokyo, Japan.
The researchers conducted a pro-
spective, open-label trial involving 204
acute ischaemic stroke patients with LVO
at 23 sites in Japan. Patients were ran-
domly assigned to the direct MT group
(MT only; n=101, median age 74 years,
55 percent male) or bridging group (MT
with tPA; n=103, median age 76 years,
70 percent male). The primary endpoint
of the study was a modified Rankin Scale
(mRS) score of 0–2 at 90 days. [ISC
2020, LB18]
Results showed that mRS score of
0–2 at 90 days was achieved by a sim-
ilar percentage of patients who had di-
AHA photo
Dr Kentaro Suzuki
CONFERENCE COVERAGE
rect MT therapy or bridging therapy (59.4
percent vs 57.3 percent; odds ratio,
1.09, 95 percent confidence interval
[CI], 0.63–1.90; p=0.17 for noninferiority,
which exceeded the noninferiority margin
of 0.74).
With regard to safety, a significantly
lower rate of intracranial haemorrhage
(ICH) was observed in the direct MT
group compared with the bridging group
within 36 hours after onset (34 percent
vs 50 percent; hazard ratio, 0.50, 95 per-
cent CI, 0.28–0.88; p=0.02).
“We could not prove noninferiority
of direct MT to bridging therapy [in this
study] … as the frequency of favourable
outcome due to high recanalization rate
was higher than [what] we expected,”
said Suzuki. “[However, the] frequency
of favourable outcomes did not differ
between [groups] … any ICH was sig-
nificantly less frequent in [the] direct MT
group.”
“We feel that giving alteplase [the
most commonly administered tPA] to
dissolve clots is not necessary, and me-
32
DOCTOR | APRIL ISSUE
chanical clot removal can be performed
immediately,” Suzuki said. “If we skip al-
teplase, we can perform MT with low risk
of bleeding.”
“The best strategy is usually to treat
with [alteplase] … and then if the patient is
eligible, the patient goes for endovascular
therapy as well,” said Professor Mitchell
Elkind from Columbia University Medical
Center of the NewYork-Presbyterian Hos-
pital in New York, US, and president-elect
of the American Heart Association (AHA),
in a press release. “But [we] don’t skip
that initial step because sometimes the
endovascular therapy [or direct MT ther-
apy] gets delayed or doesn’t occur for
some reason or another.”
“[T]he AHA/American Stroke Asso-
ciation [currently] recommends using IV
therapy within the 4.5 hour-time window
and then treating with mechanical clot
removal, if appropriate,” Elkind added.
* SKIP: Randomized study of endovascular therapy
with versus without intravenous tissue plasminogen
activator in acute stroke with ICA and M1 occlusion
- A prospective, multicenter, randomized trial
** LVO: Large vessel occlusion

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Endovascular treatment offers hope for
ischaemic stroke from basilar artery occlusion
AUDREY ABELLA
T
he addition of endovascular treat-
ment (EVT) to standard medical
treatment (SMT) in patients with
acute ischaemic stroke (AIS) attributable to
basilar artery occlusion (BAO) was asso-
ciated with improved functional outcomes
and reduced mortality, according to the
results of the nonrandomized, prospective
BASILAR* study presented at ISC 2020.
Acute BAO is rare but potentially dev-
astating with severe disability and mortality
rates. [Stroke 2009;40:3834-3840; Lan-
cet Neurol 2011;10:1002-1014] Despite
previous studies on acute BAO, most are
limited by small populations, single-arm
designs, and use of outdated EVT tech-
niques. [JAMA Neurol 2016;73:1225-
1230; Stroke 2017;48:3252-3257]
Several trials have established the effi-
cacy and safety of EVT for AIS in the anterior
circulation. [N Engl J Med 2018;378:708-
718; N Engl J Med 2018;378:11-21] How-
ever, it remains unclear whether the benefit
may translate to acute BAO, noted the re-
searchers.
The researchers evaluated the im-
pact of EVT in 829 consecutive patients
(73.8 percent male, median age 65 years)
presenting with an acute symptomatic
and radiologically confirmed BAO. Par-
ticipants received SMT** either with (EVT
arm; n=647) or without EVT*** (SMT
arm; n=182). [ISC 2020, abstract LB17;
JAMA Neurol 2020;doi:10.1001/jamaneu-
rol.2020.0156]
A substantial improvement in the 90-
day functional outcomes was observed in
the EVT vs the SMT arm (adjusted com-
mon odds ratio [adjcOR], 3.08; p<0.001).
“Our study showed that, in real-world prac-
tice, patients with AIS and confirmed acute
symptomatic BAO appear to benefit with
CONFERENCE COVERAGE
respect to functional recovery when EVT is
administered within 24 hours of estimated
occlusion time,” said the researchers.
Compared with the SMT arm, the EVT
arm had a significantly higher fraction of
participants achieving a modified Rankin
Scale (mRS) score of ≤3 (32 percent vs
9.3 percent; adjusted OR [adjOR], 4.70;
p<0.001) and a lower mortality rate (46.2
percent vs 71.4 percent; adjOR, 2.93;
p<0.001) despite an upsurge in the rate
of symptomatic intracerebral haemorrhage
(sICH) at 90 days (7.1 percent vs 0.5 per-
cent; p<0.001).
The 90-day mRS ≤3 outcomes sug-
gest that the likelihood of walking inde-
pendently was higher with EVT recipients,
noted the researchers.
Despite the low mortality rate in the EVT
arm, this was relatively higher compared
with previous reports. [J Am Heart Assoc
2018;doi:10.1161/JAHA.118.009419; Eur
J Neurol 2019;26:299-305] “[This] could
be explained by the delayed observed
reperfusion times and the severity of stroke
deficits, both well-known factors for worse
prognosis,” explained the researchers.
The sICH rate with EVT, albeit high,
was lower than that reported in the BA-
SICS# registry. [Lancet Neurol 2009;8:724-
730] “[This] probably reflects the more ad-
vanced intervention techniques available
today,” they added.
More than a quarter (27.5 percent) of
EVT recipients had good outcomes (mRS
scores ≤2). While this appears low com-
pared with evidence reflecting higher rates,
[Radiology 2019;291:730-737; J Neuro-
surg 2018;129:1482-1491] the fraction
of participants with large-artery athero-
sclerosis stroke (64.6 percent, 20.3 per-
cent of whom exhibiting good outcomes)
in the current study should be taken into
33
DOCTOR | APRIL ISSUE
account. Given the poor outcomes tied to
BAO, the observed mRS scores seem rel-
atively favourable, the researchers pointed
out.
“[O]ur study contributes evidence to
support the safety and efficacy of EVT
for patients with AIS caused by BAO who
could be treated within 24 hours of esti-
mated occlusion time … [Therefore,] EVT
should be considered in addition to SMT in
selected patients [in this setting],” said the
researchers.
The findings are even more important
given the paucity of data comparing the
outcomes of the two treatment strategies,
as well as the challenges that come with
randomization in this patient subset, they
added. [Interv Neuroradiol 2020;26:5-6]
Despite the greater fraction of patients
in the EVT vs the SMT arm, the study is a
good representation of daily clinical prac-
tice for patients with acute symptomatic
BAO, noted the researchers. “[Our study]
constitutes one of the best available data
about BAO treatment [despite its limita-
tions].”
Further insight
While the results contradict those in BA-
SICS, the researchers are anticipating up-
dates from this study, as well as from the
BAOCHE## trial. “[BASICS] was concluded
10 years ago … [Therefore,] its findings
may not be applicable to current practice.”
* BASILAR: EVT for Acute BAO study
** intravenous thrombolysis with recombinant
tissue plasminogen activator or urokinase,
antiplatelet agents, systematic anticoagulation, or
combinations of these treatments
*** mechanical thrombectomy with stent retrievers
and/or thrombo-aspiration, balloon angioplasty,
stenting, intra-arterial thrombolysis, or
combinations of these approaches
# BASICS: BASilar artery International Cooperation
Study
## BAOCHE: Basilar Artery Occlusion: CHinese
Endovascular trial
 CONFERENCE COVERAGE
International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US

Point of care MRI feasible for stroke detection

TRISTAN MANALAC Notably, even if no caution was taken

T
he use of a portable, low-field
magnetic resonance imaging (MRI)
system is safe and viable for the
bedside diagnosis of stroke, according
to a new study presented at ISC 2020.
“We started this research several
years ago because obtaining accessible
to remove traces of and equipment with
ferrous material in the room, no evidence
of interference with the static field, gra-
dient, and radiofrequency pulses of the
bedside machine were detected. There
were also no reports of significant ad-
verse events due to the scanning.
For the remaining 11 patients, the point

and meaningful brain imaging for patients
has been a major worldwide healthcare
gap for decades,” said Dr Kevin Sheth,
senior author and chief physician, Divi-
sion of Neurocritical Care and Emergen-
cy Neurology at Yale School of Medicine
and Yale New Haven Hospital in Con-
necticut, US in a press statement. “The
whole thing works because we are using
low-field magnets to acquire brain imag-
es after a stroke.”
“This early work
suggests our approach
is safe and viable in a
complex clinical care
environment”
of care MRI technology was unsuitable.
Five of these participants (6 percent over-
all) were too big for the machine and were
unable to fit through the scanner’s 30-cm
opening. The six other patients (7 percent
overall) opted to terminate the exam early,
complaining of claustrophobia.
In the present study, the point of care
scans were performed in Yale’s Neuro-
science Intensive Care Unit. The bedside
machine was powered by a standard
110-V, 15-A power outlet. The room envi-
ronment included other equipment, such
as vitals monitor, ventilators, and intrave-
nous infusion pumps; these were left as
they were, testing the ability of the bed-
side MRI to function in a typical setting.
AHA photo
Dr Kevin Sheth
“We’ve flipped the concept from hav-
ing to get patients to the MRI to bring-
ing the MRI to the patients,” said Sheth.
“This early work suggests our approach
is safe and viable in a complex clinical
care environment.”
“There’s a lot of work to do. However,
we’ve cracked the door open for bring-
ing this technology to any setting, any-
where: In rural settings, urban advanced
hospitals, and in remote villages in areas
of the world where it’s hard to get an MRI
– not anymore,” he added.

Researchers enrolled 85 stroke pa-

tients (age 18–96 years, 46 percent fe-
male), in whom point of care MRI was
applied. The median National Institutes
of Health Stroke Scale (NIHSS) score
was 7, with values ranging from 1–29;
body mass index values ranged from
20.0–46.5 kg/m2. Scans were obtained
within 7 days of symptom onset. [ISC
2020, abstract 57]

Eighty-seven percent (n=74) of the

participants were able to complete the
bedside test, with a mean exam time of
28.9 minutes, suggesting good interven-
tion feasibility.

34
DOCTOR || APRIL ISSUE

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Wearable brain stimulation device shows
promise for motor function recovery after stroke
PEARL TOH
A
novel, noninvasive, wearable
brain stimulation device that deliv-
ers continuous transcranial mag-
netic stimulation to induce the brain to
rewire itself significantly increases brain
activity and is safe in patients with chron-
ic ischaemic stroke — thus presenting a
step forward to improving motor function
after stroke, suggests a preliminary study
presented at ISC 2020.
The wearable device, which trans-
mits transcranial rotating permanent
magnet stimulation (TRPMS), significant-
ly enhanced brain activity by nine times
compared with sham treatment in brain
areas near the injured sites, as measured
by functional MRI (fMRI).
“The robustness of the increase in
physiological brain activity was surpris-
ing. With only 30 subjects, a statistical-
ly significant change was seen in brain
activity,” said lead study author Dr David
Chiu, director of the Eddy Scurlock
Stroke Center at Houston Methodist
Hospital in Houston, Texas, US.
Compared with sham control, active
TRPMS led to significantly more active
voxels immediately after stimulation in
the same side of the brain as the stroke
lesion (median, 227.5 vs 26; p=0.016).
AHA photo
Dr David Chiu
CONFERENCE COVERAGE
Voxels are burst of orange specks on
fMRI that are indicative of brain activity.
[ISC 2020, abstract LB3]
Notably, the difference between
groups on fMRI remained significant even
one month after treatment (p=0.024).
Furthermore, the intensity of the ac-
tive voxels was also significantly greater
after TRPMS than sham (median, 5.87 vs
4.86; p=0.008).
“The treatment effect on the prima-
ry endpoint [of active voxel number] was
not significantly influenced by age, time
after stroke, or cortical vs subcortical
lesion location,” reported Chiu. “[Also,]
TRPMS treatment was well tolerated
with no device-related adverse effects.”
For the secondary endpoint of motor
function, gait velocity was significant-
ly improved immediately after active
TRPMS vs sham treatment, as assessed
on the Timed Up and Go (TUG) scale
(p=0.03). The improvement persist-
ed through 1 (p=0.006) and 3 months
(p=0.002) post-treatment.
Improvements were also seen in four
out of five other measures of motor func-
tion, including grip strength, NIH* Stroke
Scale, Fugl-Meyer Upper Extremity (FM-
UE), and action research arm test (ARAT),
although the difference did not reach sta-
tistical significance between groups.
“[The] clinical scales suggested pos-
sible improvement of motor function
which persisted for 3 months after treat-
ment,” observed Chiu.
The double-blind phase I/IIA sin-
gle-centre study randomized 30 patients
(median age 66 years, 48 percent male)
with chronic ischaemic stroke to bilater-
al hemispheric active TRPMS or sham
35
DOCTOR | APRIL ISSUE
treatment over 20 sessions, 40 minutes
each spanning through 4 weeks.
Although the study was too small to
show clinical benefit, Professor Mitchell
Elkind, AHA** president-elect from Co-
lumbia University New York in New York,
New York, US, noted that “it wasn’t real-
ly intended to show that and there were
suggestive benefits even in clinical out-
comes also,” in an accompanying mul-
timedia.
“We’re still just
beginning to crack open
the possibility of what
we can do around stroke
recovery”
“Recovery is really, what I think of
as the black box of stroke manage-
ment. You know, we’ve gotten good at
stroke prevention [and] more recently …
at acute interventions like endovascular
therapy. But we’re still just beginning to
crack open the possibility of what we can
do around stroke recovery, and promot-
ing brain reorganization after someone
has a stroke,” he commented.
The advantage of a wearable TRPMS
device is that patient could potentially
apply the treatment at home without hav-
ing to visit the clinic, pointed out Elkind.
“If confirmed in a larger multicentre
trial, the results would have enormous
implications. This technology would be
the first proven treatment for recovery of
motor function after chronic ischaemic
stroke,” Chiu said.
* NIH: National Institutes of Health
** AHA: American Heart Association

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Could prompt tranexamic acid treatment reduce
ICH growth?
ROSHINI CLAIRE ANTHONY
P
rompt treatment with tranexamic
acid may reduce intracerebral hae-
morrhage (ICH) growth in patients
with ongoing bleeding, though the timing
of treatment appears to be key to im-
proved outcomes, according to a study
presented at ISC 2020.
“[Tranexamic acid]
treatment led to a
non-statistically
significant reduction
in ICH growth”
The phase II STOP-AUST* trial in-
volved 100 patients with ICH who exhib-
ited a spot sign – a marker of ongoing
bleeding – on computed tomography (CT)
angiography. They were randomized 1:1
to receive either intravenous tranexamic
acid (1 g over 10 minutes followed by 1 g
over 8 hours; median age 72.5 years, 30
percent female) or placebo (median age
71 years, 46 percent female) within 4.5
hours of ICH onset (median time to treat-
ment 150.5 minutes). Median NIHSS** at
baseline was 14 and 12 in the tranexam-
ic acid and placebo groups, respectively,
while median ICH volume was 13.8 and
15.6 mL, respectively.
AHA photo
Dr Nawaf Yassi
CONFERENCE COVERAGE
ICH growth – defined as a >33 per-
cent or >6 mL increase from baseline in
24 hours after adjustment for baseline
ICH volume – occurred in 44 and 52 per-
cent of patients who received tranexamic
acid and placebo, respectively (adjusted
odds ratio [adjOR], 0.72, 95 percent con-
fidence interval [CI], 0.32–1.59; p=0.41).
[ISC 2020, abstract LB20]
Absolute haematoma growth was
numerically, but not significantly, reduced
in tranexamic acid vs placebo recipients
(median 1.9 vs 3.4 mL; adjusted median
difference -1.8 mL, 95 percent CI, -5.2 to
1.5 mL; p=0.28).
“[Tranexamic acid] treatment led to
a non-statistically significant reduction
in ICH growth, both in binary and abso-
lute terms,” said study author Dr Nawaf
Yassi from the University of Melbourne in
Parkville, Victoria, Australia.
Subgroup analyses noted a trend
toward reduced haematoma growth
among the 66 patients who received
treatment ≤3 hours of ICH onset (adjOR,
0.41, 95 percent CI, 0.15–1.12), but not
among those who received treatment
3–4.5 hours after onset (adjOR, 2.45, 95
percent CI, 0.52–11.57; pinteraction=0.06).
Post hoc analyses suggested that
the best outcomes were derived when
patients received tranexamic acid ≤2
hours from ICH onset (OR, 0.19, 95 per-
cent CI, 0.03–1.15; p=0.07), with the risk
reduction less apparent when treatment
was administered at <3 hours (OR, 0.41)
and <4 hours (OR, 0.64) from onset.
“Further trials using tranexamic acid
are ongoing and focusing on ultra-early
treatment – within 2 hours. This is where
the greatest opportunity for intervention
appears to be,” said Yassi.
36
DOCTOR | APRIL ISSUE
There was no difference between
tranexamic acid and placebo recip-
ients in terms of major thromboem-
bolic events (n=1 and 2, respectively;
OR, 0.49; p=0.57), though there was
a nonsignificant higher mortality rate in
the tranexamic acid group (n=13 vs 8;
adjOR, 2.38; p=0.19).
“We have to get
to those patients super
early, perhaps even earlier
than we’re accustomed
to doing for ischaemic
stroke patients”
“I think a big reason for these kinds
of results in the setting of haemorrhage is
that, very quickly after the haemorrhage
begins and the haematoma expands a
bit, a lot of damage may already have
occurred. And so even if we stop the
bleeding later, much of the injury has oc-
curred, and it may just be a bit too late.
But the proof of principle is there,” said
Professor Mitchell Elkind from Colum-
bia University, New York City, New York,
US, and president-elect of the American
Heart Association, who was not affiliated
with the study.
“[I]n a sense [this is] a very exciting re-
sult because it suggests that we may be
able to have an impact, although from a
practical level, it means we have to get to
those patients super early, perhaps even
earlier than we’re accustomed to doing
for ischaemic stroke patients. And that
I think is [going to] be the big challenge
with a lot of these therapies,” he added.
* STOP-AUST: The Spot Sign and Tranexamic Acid on
Preventing ICH Growth – Australasia Trial
** NIHSS: National Institutes of Health (NIH) Stroke
Scale

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
JAIRIA DELA CRUZ
A
multicentre trial to investigate
whether antithrombotic therapy
can be initiated in atrial fibrilla-
tion (AF) patients who have survived an
intracerebral haemorrhage (ICH) can be
done, based on the results of the phase
II feasibility trial NASPAF-ICH* presented
at ISC 2020.
The trial “provides the first ran-
domized, albeit limited, data on clinical
outcomes according to differing anti-
thrombotic regimens in this vulnerable
population,” said lead investigator Dr
Ashkan Shoamanesh from the McMaster
University in Hamilton, Ontario, Canada.
NASPAF-ICH recruited a total of 30
patients (mean age 77 years, 43 per-
cent female) with AF and previous ICH
(≥2 weeks prior). These patients were
randomly assigned to receive standard
dosing nonvitamin K oral anticoagulants
(NOACs, n=21; 76 percent received
apixaban and 24 percent received dabig-
atran) or aspirin 81 mg (n=9) daily. None
of them had ≥2 prior symptomatic lobar
ICH, contraindications to aspirin/NOACs,
and/or glomerular filtration rate of <30
mL/min/1.73/m2.
Recruitment rate, the primary feasi-
bility outcome, was 3.1 per site per year
CONFERENCE COVERAGE
NASPAF-ICH:
Multicentre antithrombotic
therapy trial feasible
for ICH survivors with AF
at nine sites across Canada. Baseline
median CHADS2 of the population was
2, HAS-BLED was 3, and MoCA was
25. Qualifying ICH was deep in most pa-
tients (60 percent), lobar in 30 percent,
and involved both regions in 10 percent.
Intracerebral bleed occurred a median of
127 days prior to randomization, with 60
percent of cases occurring while on an-
ticoagulation. [ISC 2020, abstract LB13]
All patients completed follow-up,
with a median duration of 13.5 months.
Four patients (13.3 percent) discontin-
ued treatment temporarily (one patient in
the aspirin group and three in the NOAC
group), and two (6.7 percent) withdrew it
permanently (both in the aspirin group).
Mean achieved blood pressure was
127/75 mm Hg.
The primary efficacy outcome of the
composite of ischaemic stroke and re-
current ICH was recorded in one aspi-
rin-treated patient (3 percent). The rate of
all-cause mortality was 10 percent (two
patients on aspirin and one on NOAC,
respectively). No cases of recurrent ICH
or fatal stroke were documented.
In terms of safety, major bleeding
occurred in one aspirin-treated patient.
Hospitalization rate was 36.6 percent
(three patients on aspirin and eight on
NOAC).
37
DOCTOR | APRIL ISSUE
“Optimal antithrombotic manage-
ment in ICH survivors with AF poses a
challenging dilemma. Available data sug-
gest that NOACs are a promising treat-
ment option in this population,” Shoama-
nesh noted.
The present data, aside from estab-
lishing the feasibility of a controlled trial
evaluating the efficacy and safety of
NOACs vs aspirin, showed that NOACs
are potentially safe for stroke prevention
in ICH survivors with AF, he added.
NASPAF-ICH paved the way for
**ENRICH-AF, a follow-up global phase III
randomized trial of edoxaban vs nonanti-
coagulant medical therapy in 1,200 par-
ticipants that is currently under way at
multiple sites in 23 countries across five
continents.
Shoamanesh acknowledged several
limitations of the trial, including the ex-
ploratory nature of clinical outcomes and
the limited generalizability of the results,
given the tight blood pressure control
noted in the population and the recruit-
ment being restricted to Canada-based
individuals.
* Non-vitamin K Oral Anticoagulants in Intracerebral
Hemorrhage Survivors With Atrial Fibrillation-
Intracranial Hemorrhage
** EdoxabaN foR IntraCranial Hemorrhage Survivors
with Atrial Fibrillation

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Stroke prevention another benefit
of shingles vaccine
ROSHINI CLAIRE ANTHONY
V
accination against herpes zoster
(shingles) with the Zoster Vaccine
Live (ZVL) vaccine may reduce the
risk of stroke in older adults, according to
a study presented at the recent ISC 2020
conference.
The researchers conducted a pop-
ulation-based study using data of
1,382,051 Medicare beneficiaries aged
≥66 years with no history of stroke and
who received ZVL between 2008 and
2014. They were compared with a con-
trol group comprising the same number
of individuals who had not received ZVL.
Over a median 3.9-year follow-up pe-
riod, a total of 42,267 strokes occurred
among individuals who received ZVL, in-
cluding 33,510 acute ischaemic strokes
and 4,318 haemorrhagic strokes over
5,890,113 person-years. In the control
group, 48,139 strokes occurred, in-
cluding 39,334 acute ischaemic strokes
and 4,713 haemorrhagic strokes over
5,693,943 person-years.
The risk of stroke was reduced by
16 percent among individuals who re-
ceived ZVL compared with the control
group (crude incidence, 7.18 vs 8.45 per
CONFERENCE COVERAGE
1,000 person-years; p<0.001; adjusted
hazard ratio [adjHR], 0.84, 95 percent
confidence interval [CI], 0.83–0.85). [ISC
2020, abstract TP493]
This reduced stroke risk among
ZVL recipients vs nonrecipients applied
to both acute ischaemic stroke (crude
incidence, 5.40 vs 6.53 per 1,000 per-
son-years; p<0.001; adjHR, 0.82, 95
percent CI, 0.81–0.83) and haemor-
rhagic stroke (crude incidence, 0.73 vs
0.82 per 1,000 person-years; p<0.001;
adjHR, 0.88, 95 percent CI, 0.84–0.91).
While the reduced stroke incidence
following ZVL administration appeared
consistent regardless of sex and race,
individuals aged 66–79 years may have
derived greater benefit compared with
those aged ≥80 years, with an almost
20 percent stroke risk reduction among
those aged <80 years and an approxi-
mate 10 percent reduction in those aged
≥80 years (pinteraction=0.020).
An association between shingles
and an increased risk of stroke has been
demonstrated in previous research. [J
Am Coll Cardiol 2017;70:295-296]
“The reason for increased risk of
stroke after a shingles infection may be
38
DOCTOR | APRIL ISSUE
due to inflammation caused by the virus,”
said lead author of the present study Dr
Quanhe Yang from the Centers for Dis-
ease Control and Prevention (CDC), At-
lanta, Georgia, US.
“Our study results may encourage
people ages 50 [years] and older to fol-
low the recommendation and get vacci-
nated against shingles. You are reducing
the risk of shingles, and at the same time
you may be reducing your risk of stroke,”
noted Yang.
Yang highlighted that while ZVL re-
duces the risk of shingles by about 51
percent, its effect decreases with age.
In addition, the present study was car-
ried out when ZVL was the only shingles
vaccine available. The currently avail-
able adjuvanted, non-live recombinant
shingles vaccine is highly effective (two
doses confer >90 percent protection) in
preventing shingles and is the CDC-rec-
ommended vaccine for adults aged ≥50
years.
Future research is warranted to not
only establish the findings of the present
study, but also to assess if the adjuvant-
ed, non-live recombinant shingles vac-
cine is also associated with a stroke risk
reduction.
 CONFERENCE COVERAGE
International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US

Diabetic retinopathy linked to

higher risk of stroke
STEPHEN PADILLA

D
amage to small blood vessels of
the eye appears to be a signifi-
cant marker for an increased risk
of stroke in patients with diabetes, sug-
gesting that the microvascular patholo-
gy inherent to diabetic retinopathy may
have greater cardiovascular implications,
according to a study presented at ISC
2020.

“A build-up of plaque in large arteries

feeding the brain and the common heart
arrhythmia atrial fibrillation are the primary
causes of ischaemic strokes, and dam-
age to small blood vessels also causes
stroke and vascular dementia, so we
thought that diabetic retinopathy might
be an important biomarker of stroke risk
for patients with diabetes,” said Ka-Ho
Wong, lead author and clinical research
coordinator and lab manager of the de
Havenon Lab at the University of Utah
Health Hospitals and Clinics in Salt Lake
City, Utah, US, in a press statement by
ASA.
Wong and colleagues conducted
a secondary analysis of a subgroup of
patients enrolled in the ACCORD Eye
Study. Stroke during follow-up was the
primary outcome. The primary predictor
was the presence of diabetic retinopathy
on the Early Treatment Diabetic Retinop-
athy Study Severity Scale as assessed
from seven-field stereoscopic fundus
photographs at baseline. Adjusted Cox
models were fit to the primary outcome
to estimate hazard ratios (HRs) for stroke.
Of the 2,828 patients (mean age 62.1
years, 61.8 percent male) included in the
study, 117 had suffered stroke during a
mean follow-up of 5.4 years. At baseline,
874 patients (30.9 percent) presented
with diabetic retinopathy, which ap-
peared to be more common in patients
with stroke compared with those without
(41.0 percent vs 30.5 percent; p=0.016).
[ISC 2020, abstract 154]
The association between diabet-
ic retinopathy and incident stroke (HR,
1.60, 95 percent confidence interval [CI],
1.10–2.32; p=0.015) persisted in the Cox
model, adjusted for baseline patient age,
gender, race, total cholesterol, glycated
haemoglobin, smoking, and randomiza-
tion arm. This association was not influ-
enced by randomization to the ACCORD
glucose intervention (p=0.305), lipid in-
tervention (p=0.546), or blood pressure
intervention (p=0.422).
“We were surprised that none of the
ACCORD interventions decreased dia-
betic retinopathy and stroke risk, espe-
cially intense blood-pressure reduction,
since a lot of microvascular diseases are
caused by high blood pressure,” Wong
said in a statement. “This finding is in
line with results from ACCORD, which
showed no reduction in heart attacks.”
Despite these findings, patients with
diabetic retinopathy were advised to re-
ceive “aggressive medical management”
to lower the risk of stroke, according to
the researchers.
The ASA recommends the follow-
ing to reduce the risk of stroke: healthy
lifestyle, including low salt intake; regu-
lar physical activity; healthy weight; to-
bacco avoidance; stress management;
limited alcohol intake (<1 drink per day
for women and 2 drinks per day for
men); and adherence to medication as
prescribed for high blood pressure, di-
abetes, high cholesterol, and atrial fibril-
lation.
“Diabetic retinopathy is a common
microvascular complication of diabetes,”
the researchers said. “Previous research
has shown that the macrovascular com-
plications of diabetes, including stroke,
are often comorbid with shared and,
possibly, synergistic pathology.”

39
DOCTOR | APRIL ISSUE

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Is there a role for nerinetide following
ischaemic stroke?
ROSHINI CLAIRE ANTHONY
T
he eicosapeptide nerinetide did
not improve outcomes in patients
with large vessel occlusion-related
acute ischaemic stroke who underwent
endovascular thrombectomy (EVT). How-
ever, patients not treated with alteplase
appeared to derive some benefit, results
from the multinational ESCAPE-NA1* trial
showed.
“Although we did not observe a
treatment benefit of nerinetide for the
primary outcome in the trial population
as a whole, a large absolute benefit was
observed for patients who received ner-
inetide and were not treated with usu-
al-care alteplase. This surprising finding
is evidence of a modification of the effect
of nerinetide, possibly due to a drug–
drug interaction between nerinetide and
alteplase,” said the authors led by Profes-
sor Michael Hill from the Foothills Medical
Centre (FMC), University of Calgary, Cal-
gary, Canada.
Within 12 hours of symptom onset,
1,105 adults with a disabling acute isch-
aemic stroke due to large vessel occlu-
sion (ASPECTS** 5–10; NIHSS*** >5)
were randomized to receive either a sin-
gle dose of intravenous (IV) nerinetide (2.6
mg/kg [270 mg max based on weight];
n=549, mean age 71.5 years, 48.8 per-
cent female) or placebo (n=556, mean
age 70.3 years, 50.5 percent female).
EVT was attempted in all patients, and
IV alteplase was administered as indi-
cated (60.1 and 59.2 percent of patients
assigned to nerinetide and placebo, re-
spectively).
Functional independence at 90 days
(modified Rankin Scale [mRS] score 0–2)
was achieved by a comparable num-
ber of patients who received nerinetide
and placebo (61.4 percent vs 59.2 per-
CONFERENCE COVERAGE
cent; adjusted risk ratio [adjRR], 1.04,
95 percent confidence interval [CI],
0.96–1.14; p=0.35). [ISC 2020, abstract
LB2; Lancet 2020;doi:10.1016/S0140-
6736(20)30258-0]
A similar proportion of patients on
nerinetide and placebo achieved NIHSS
0–2 (58.3 percent vs 57.6 percent; adjRR,
1.01), as well as functional independence
in activities of daily living (Barthel index
score ≥95; 62.1 percent vs 60.3 percent;
adjRR, 1.03), and excellent functional
outcome (mRS 0–1; 40.4 percent vs 40.6
percent; adjRR, 0.98). There were 67 and
80 deaths in the nerinetide and placebo
groups, respectively.
Serious adverse events (AEs) oc-
curred at a comparable rate between
groups (33.1 percent vs 35.7 percent for
nerinetide vs placebo). The most com-
mon AEs among nerinetide recipients
were stroke-in-evolution (6.6 percent),
pneumonia (4.6 percent), symptomatic
intracranial haemorrhage (3.5 percent),
and new or recurrent ischaemic stroke
(3.3 percent).
Improvements in the absence
of alteplase
Exploratory analyses showed that among
the 446 patients who did not receive al-
teplase, nerinetide conferred improve-
ments in functional independence and
mortality at 90 days vs placebo (mRS
score 0–2: 59.3 percent vs 49.8 percent;
adjRR, 1.18, 95 percent CI, 1.01–1.38;
mortality: 7.5 percent absolute risk re-
duction; adjusted hazard ratio, 0.56,
95 percent CI, 0.35–0.95). Conversely,
there was no between-group difference
in achieving mRS score 0–2 among pa-
tients who received alteplase.
“Compared to placebo, almost 20
percent more patients who received neri-
netide along with endovascular treatment,
40
DOCTOR | APRIL ISSUE
but did not receive alteplase, recovered
from a devastating stroke – a difference
between paralysis and walking out of the
hospital,” said Hill. “In the patients who
received both drugs, the alteplase negat-
ed the benefits of the nerinetide.”
In the no-alteplase group, median in-
farct volume was lower with nerinetide vs
placebo, with no between-group differ-
ence among alteplase recipients. There
was also no between-group difference in
terms of infarct volume based on endo-
vascular device.
According to the researchers, the
improvements with nerinetide in the
no-alteplase group appear to rule out “a
chance finding”, though further research
is required to confirm this. “The absence
of benefit of nerinetide in the alteplase
stratum is likely to be due to enzymatic
cleavage of nerinetide by plasmin, lead-
ing to subtherapeutic concentrations of
nerinetide,” they suggested.
A new therapeutic option?
“We really believe this is a new scientif-
ic observation,” noted Hill. “There is ev-
idence nerinetide promotes brain cell
survival, offering neuroprotection until we
can extract the clot. It opens the door to
a new way of treating stroke.”
“After so many studies investigating
neuroprotective drugs failed, we are ex-
tremely excited by these results. While
nerinetide is not approved for use yet,
it shows the potential of a new tool to
promote recovery from stroke,” added
co-author Professor Mayank Goyal, also
from FMC.
* ESCAPE-NA1: Safety and efficacy of NA-1 in
subjects undergoing endovascular thrombectomy
for stroke
** ASPECTS: Alberta Stroke Program Early CT Score
*** NIHSS: National Institutes of Health Stroke Scale

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
EXTEND-IA TNK: 0.25 mg/kg tenecteplase
sufficient for large vessel stroke
PEARL TOH
T
he lower 0.25 mg/kg dose of the
thrombolytic tenecteplase may be
sufficient for reperfusion of blocked
vessels prior to thrombectomy in patients
with ischaemic stroke due to large vessel
occlusion compared with the 0.4 mg/kg
dose, according to the EXTEND-IA TNK*
Part 2 study presented at the ISC 2020
meeting.
“There was no
advantage to
increasing the dose
beyond 0.25 mg/kg”
“The two doses behaved very similar-
ly overall, and there was no advantage to
increasing the dose beyond 0.25 mg/kg
in this study,” said Dr Bruce Campbell of
the Royal Melbourne Hospital in Parkville,
Australia. “These results provide reassur-
ance that there is a window of safety if
the weight-based dose is inadvertently
overestimated.”
Tenecteplase, a genetically modified
version of the tPA** alteplase, confers
practical clinical advantages in terms of
a convenient single-bolus administration
compared with alteplase which entails a
1-hour infusion after the initial bolus.
Tenecteplase has been suggested as
an alternative to alteplase in the AHA***
2019 stroke guidelines (level IIb recom-
mendation) based on evidence of nonin-
feriority in a meta-analysis. However, the
dose recommendations are confusing: a
lower dose of 0.25 mg/kg for large vessel
occlusions and a higher dose of 0.4 mg/
kg for mild stroke without large vessel oc-
clusions.
CONFERENCE COVERAGE
“The objective of part 2 of the EX-
TEND-IA TNK trial was to clarify the op-
timal dosage of tenecteplase in patients
with ischaemic stroke,” the investigators
said. “To our knowledge, this study is
the first substantial head-to-head com-
parison of the two candidate doses of
tenecteplase for ischaemic stroke.”
Compared with 0.4 mg/kg tenect-
eplase, the same proportion of patients
on the 0.25 mg/kg dose achieved the
primary outcome of >50 percent reper-
fusion of the ischaemic territory (19.3
percent in each arm; adjusted risk ratio
[RR], 1.03; p=0.89). [ISC 2020, ab-
stract LBA1; JAMA 2020;doi:10.1001/
jama.2020.1511]
The proportion of patients achieving
so rose to one-third in each arm when the
analysis was restricted to patients in rural
centres (33.3 percent vs 35.0 percent;
p=0.76).
“About 34 percent of patients treated
in rural centres had substantially improved
blood flow by the time they arrived at a
hospital capable of performing mechani-
cal clot removal,” noted Campbell. “This
treatment could be particularly important
for them … [as] bridging thrombolysis +
thrombectomy remains standard of care
for eligible patients with large-vessel oc-
clusion.”
There was also no significant differ-
ences in functional outcomes between
the two arms, as indicated by mRS#
score at 90 days (adjusted odds ratio,
0.96; p=0.73), functional independence
(RR, 1.08; p=0.40), and freedom from
disability (RR, 1.04; p=0.69).
While the rate of symptomatic intra-
cranial haemorrhage was numerically
higher in the 0.4 mg/kg arm (4.7 percent
vs 1.3 percent in the 0.25 mg/kg arm),
41
DOCTOR | APRIL ISSUE
AHA photo
Dr Bruce Campbell
the difference was largely associated with
wire perforations during thrombectomy
(rather than dose difference) — account-
ing for four out of the seven events in the
0.4 mg/kg arm.
“I think the study really kind of settles
the dose that might be used of tenect-
eplase, when used together with endo-
vascular therapy, at 0.25 mg/kg,” stated
Dr Mitchell Elkind of Columbia University
in New York, New York, US, who serves
as AHA president-elect.
The multicentre, open-label trial ran-
domized 300 patients with ischaemic
stroke due to large vessel occlusion to re-
ceive 0.40 mg/kg or 0.25 mg/kg tenect-
eplase in a 1:1 ratio, prior to endovascu-
lar thrombectomy.
Although the study population com-
prised patients with ischaemic large-ves-
sel stroke who were eligible for thrombol-
ysis, Campbell believed that it is unlikely
that nonlarge vessel occlusion patients
would require higher dose.
“The lack of benefit of the increased
dose of tenecteplase in this study could
be reasonably extrapolated to patients
with smaller vessel occlusions and lower
clot burden,” he said.
* EXTEND-IA TNK: EXTending the time for
thrombolysis in Emergency Neurological Deficits -
Intra-Arterial using intravenous Tenecteplase
** tPA: tissue plasminogen activator
*** AHA: American Heart Association
# mRS: modified Rankin Scale

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Sex, genetic predisposition synergistic
for stroke, MI risks in middle-aged people
JAIRIA DELA CRUZ
B
eing male and having a high ge-
netic predisposition to sustain an
acute vascular event (AVE) predict
greater risks of stroke and myocardi-
al infarction (MI) than either factor does
alone in a population of middle-aged in-
dividuals without vascular risk factors, as
shown in a study presented at ISC 2020.
“Driven by ageing-related physio-
logical changes, the incidence of stroke
and MI rises rapidly in persons aged >40
years. A significant proportion of these
AVE take place in persons without vas-
cular risk factors,” according to a team
of investigators led by Dr Guido Falcone
from the Yale School of Medicine in New
Haven, Connecticut, US.
Guido and colleagues tested the hy-
pothesis that sex and genetic predispo-
sition synergistically increased the risk of
AVE in a UK Biobank cohort of 303,295
individuals aged 40–60 years without
vascular risk factors. They constructed
a polygenic risk score using 68 indepen-
dent (R2<0.1) genetic variants known
to be associated (p<5x10-8) with AVE,
grouping participants according to ter-
tiles of the score.
A total of 5,746 AVEs were docu-
mented, including 1,954 strokes (isch-
aemic and haemorrhagic) and 3,792
MIs. The cumulative risk of AVE accord-
ing to age was 0.12 percent at 40 years
(n=352), 0.46 percent (n=1,386) at 50
years and 1.32 percent (n=4,008) at 60
years (p-trend<0.001). [ISC 2020, ab-
stract 71]
On Cox analysis, men had a twofold
higher risk of AVE than women (hazard
ratio [HR], 3.30, 95 percent confidence
interval [CI], 3.08–3.53). In terms of ge-
netic risk, the high and intermediate risk
CONFERENCE COVERAGE
score tertiles conferred a 22-percent
(HR, 1.22, 95 percent CI 1.13–1.32) and
52-percent (HR, 1.52, 95 percent CI,
1.41–1.65) risk increase, respectively,
relative to the lowest tertile.
Sex and genetic predisposition
showed a significant synergy, such that
males with high genetic risk had about a
fourfold higher risk of AVE as compared
with females with low genetic predisposi-
tion (HR, 3.91, 95 percent CI, 3.58–4.26;
pinteraction<0.001).
In light of the present data, Guido
and his team noted that “genetic infor-
mation constitutes a promising tool to
risk stratify middle-aged persons without
vascular risk factors.
“The synergistic effect
of sex and genetic
predisposition points
to specific subgroups
that could benefit from
aggressive preventive
interventions”
42
DOCTOR | APRIL ISSUE
“The synergistic effect of sex and
genetic predisposition points to specific
subgroups that could benefit from ag-
gressive preventive interventions,” they
added.
Stroke prevention aims at reducing
the incidence through targeted modifi-
cation of a single risk factor, or a cluster
of multiple risk factors. A study defined
three broad levels of stroke prevention: 1)
primordial, which is the most generaliz-
able and involves healthy living measures
targeted to reduce the population inci-
dence of physiologic stroke risk factors;
2) primary, which is directed at improv-
ing the risk factor profile of individuals
who do not have a history of stroke or
transient ischaemic attack (TIA) in order
to prevent a first cerebrovascular event;
and 3) secondary, which is the most tar-
geted and is only implemented following
a stroke or TIA, with the goal of prevent-
ing recurrence. [Circ Res 2017;120:472-
495]

International Stroke Conference (ISC) 2020 • February 19-21 • Los Angeles, California, US
Optimistic stroke survivors
enjoy better health outcomes
TRISTAN MANALAC
O
ptimism appears to be beneficial
among stroke survivors, leading
to lower physical disability, lighter
stroke severity, and suppressed inflam-
mation, according to a new study pre-
sented at ISC 2020.
“Our results suggest that optimistic
people have a better disease outcome,
thus boosting morale may be an ideal
way to improve mental health and recov-
ery after a stroke,” according to Yun-Ju
Lai, lead author and postdoctoral fellow
in the neurology department at The Uni-
versity of Texas Health Science Centre at
Houston, Texas, US.
Forty-nine stroke survivors were en-
rolled at baseline, but by 3-month fol-
low-up, the sample size had decreased
to 13 survivors. Researchers found a
significant and negative correlation be-
tween optimism and stroke severity, as
measured by the National Institutes of
Health Stroke Scale (NIHSS; ρ, –0.41;
p=0.003). [ISC 2020, abstract WP466]
Similarly, optimistic participants
seemed to have a better inflammatory
profile. Optimism scores were negative-
CONFERENCE COVERAGE
ly and significantly correlated with bio-
markers such as interleukin-6 (ρ, –0.44;
p=0.008) and C-reactive protein (CRP; ρ,
–0.40; p=0.02). In contrast, no such as-
sociation was found for tumour necrosis
factor-α.
Physical recovery was likewise bet-
ter in optimistic survivors. Scores in the
modified Rankin scale were significantly
and inversely associated with optimism
(ρ, –0.30; p=0.05).
Notably, adjusting for potential con-
founders did not attenuate the effects
of optimism on health outcomes after
stroke. The NIHSS score, for instance,
remained associated, dropping by 0.27
points with each unit improvement in the
optimism score (p=0.001). The same
change in optimism prompted a signif-
icant 0.11-point reduction in modified
Rankin scale scores (p=0.03).
The same was true for the inflamma-
tion profile. Each unit increase in opti-
mism was correlated with a 148.6-ng/mL
decrease in CRP (p=0.02), while its effect
on interleukin-6 was attenuated. Tumour
necrosis factor-α remained unrelated.
“Optimism has been associated
43
DOCTOR | APRIL ISSUE
AHA photo
Yun-Ju Lai
with lower inflammation and better
health outcomes among people with
medical conditions, but no stud-
ies have assessed this association
in stroke population,” Lai said. “The
overall goals were to examine the re-
lationship between optimism, stroke
severity, physical disability, and inflam-
mation during hospitalization and to
evaluate this relationship over the 3-
month post-stroke period.”
In the current pilot study, partici-
pant information was retrieved from
the BioRepository of Neurological Dis-
eases biobank. Optimism was evalu-
ated using the revised Life Orientation
Test, a standard psychological tool.
Enzyme-linked immunosorbent as-
says were performed for the measure-
ment of inflammatory biomarkers.
“Although the number of patients
was low in this initial cohort, under-
standing this relationship may provide
a scientific framework whereby new
strategies for stroke recovery can be
developed,” Lai pointed out.
“Patients and their families should
know the importance of a positive en-
vironment that could benefit the pa-
tient,” she added. “Mental health does
affect recovery after a stroke.”
* ESCAPE-NA1: Safety and efficacy of NA-1 in
subjects undergoing endovascular thrombectomy
for stroke
** ASPECTS: Alberta Stroke Program Early CT Score
*** NIHSS: National Institutes of Health Stroke Scale
 HOSPITAL HOUR

DR EUGENE SOH
CEO, TTSH

Tan Tock Seng

Hospital Singapore
leading the way in digital
transformation of hospital and
pharmacy management
44
DOCTOR | APRIL ISSUE
 HOSPITAL HOUR
With its rich 175-year heritage, Tan
Tock Seng Hospital (TTSH) is one of
the pioneering institutions of medical
care and development in Singapore.
Today, the hospital, with its 1,700-
bed capacity and approximately 9,000
staff, plays a key role in providing
medical care to 1.4 million patients
in Central Singapore. In an interview
with MIMS Doctor, Dr Eugene Soh,
CEO of TTSH and Chairman of its
Centre for Healthcare Innovation
(CHI), shared his thoughts on how
digital innovation will pave the way
for pharmacy transformation, improve
the way medications are currently
managed, and enhance overall patient
experience.
Addressing the current gaps
in today’s transformation process
“Healthcare today is quickly evolving to meet the
increasing demands of today’s ageing population and the
increase in the burden of chronic diseases. Because of
this, our pharmacy also has to change in order to meet the
evolving needs of both healthcare providers and patients,”
said Soh. Soh, who is also an Adjunct Professor at the Lee
Kong Chian School of Medicine, Nanyang Technological
University (NTU), noted that first and foremost, there is a
need to move away from the current volume-based model to
a more value-based one. “This means there should be more
focus on outcomes, safety, and sustainability.” Essentially,
he said, there is a need to transition from a ‘doing more is
better’ to a ‘doing better is more’ mindset.
Secondly, today’s medication delivery system – from
prescription to administration – is driven from a facility point-
of-view, be it clinics or hospitals. “The future of medication
delivery lies with care being able to go to patients. Care should
follow the patient, and not just be restricted to the four walls
of a facility,” said Soh. With chronic diseases, he stressed, it is
important that we are constantly adding value to healthcare.
“Hence, we need to be more focused on the whole person to
deliver better care rather than focused on the facility (pharmacy)
to deliver better care; person-focused, not facility-focused.”
45
DOCTOR | APRIL ISSUE
Thirdly, Soh highlighted that the delivery of healthcare needs
to transition from the current episodic model to a relationship-
based system. “Today, care is delivered in ‘episodes’ during
clinic visits or admissions and, should any issue occur during
treatment, a lot of time is spent on reconciliation. Transitioning
to a more relationship-based model will support future care
models in today’s ageing population and the corresponding
increase in chronic diseases.”
The role of digital transformation
“Just as healthcare has been disrupted by new
technologies, so will digital transformation disrupt the
pharmacy,” said Soh. Digital transformation, he stressed,
is about how technology will be able to transform current
business models, as well as workforce models, to truly
bring about change in the system. “The key is to be able
to drive system-based innovations, and not just adopt new
technologies,” he said.
System-based innovation begins with a review and
redesign of the current care model, following which, new
technology is introduced to power the new care model,
and reduce waste in the system. “In parallel, the workforce
needs to undergo a transformation to be able to tap into
the new technology and deliver on that new model of
care.” Soh stressed that the final step – transformation of
the workforce in parallel with system innovation – is crucial
to ensure that innovation truly leads to transformation.
Global trends in innovation
within the hospital pharmacy
“Automation is fast being adopted by hospital
pharmacies as a way to meet the ever increasing workload
demands, whilst ensuring accuracy, increasing efficiency,
and reducing human error,” said Soh. The second trend,
he noted, goes beyond automation to distribution, and it is
here that distribution networks play an important role. “There
are essentially two key distribution networks involved – a
centralized network where distribution is from one central
pharmacy warehouse or a de-centralised network where
distribution is from any nearby pharmacy. Ultimately, the
decision is dependent on the resources available.
The third trend in innovation is precision medicine, and
this, Soh highlighted, is a potential game changer. “With big
data driving the science behind precision medicine, coupled
with the evolution of pharmacogenomics and population
science, this will essentially change our understanding of
diseases, patients, and the way we prescribe medicines.”
 HOSPITAL HOUR
Innovating multidisciplinary care
and empowering patients
Soh believes there are several ways in which
technology can innovate the delivery of multidisciplinary
care. “Technology can help to increase and improve
coordination of multidisciplinary teams and this may help
to reduce the number of medications patients have to be
on,” said Soh. “It can also play a crucial role in empowering
patients to take ownership of their medication and
treatment journey.”
Innovating the pharmacy
to ensure error-free medication
“There are so many factors and rules physicians have
to take into consideration with regards to medications,
from the patient’s diagnosis to contraindications. As such,
the implementation of a clinical decision support (CDS)
tool to guide medication prescribing and use can help
aid medical staff to make the best decisions that will best
serve patients,” said Soh.
It provides healthcare practitioners (including doctors and
pharmacists) with timely and regularly updated prescribing
information on pharmaceutical products. Importantly, it
provides healthcare practitioners with clear warnings on
46
DOCTOR | APRIL ISSUE
drug-drug interactions, as well as warnings about potential
drug allergies. It also generates a cross-reaction warning for
allergic cross sensitivity between drug groups.
“At the same time, this CDS tool also represents
a learning community of practice whereby medical
evidence can be used to inform current practices, and
further aid better decision-making in medication use.
It can also alert us as to where potential problems may
arise,” said Soh. Ultimately, he noted, it’s not just about
improving basic clinical decision-making such as adverse
effects management, the innovation has to extend to the
individual level so there is innovation and learning across
the community, which will lead to an overall improvement
in practice within the organization, and that will in turn
translate to better patient management.
With big data driving the science
behind precision medicine, coupled
with the evolution of genomics
and population science, this will
essentially change our understanding
of diseases, patients and the way we
prescribe medicines
– Dr Eugene Soh
Photo courtesy of Tan Tan Tock Seng Hospital
 IN BRIEF

Novel PET-CT method superior to

conventional imaging in detecting high-risk
localized prostate cancer
PANK JIT SIN imaging was performed within 21 days PSMA PET-CT also proved to be supe-

A
novel imaging technique using
prostate-specific membrane an-
tigen positron emission tomog-
raphy – computed tomography (PSMA
PET-CT) is a suitable replacement
for conventional imaging, a study re-
veals. [Lancet doi.org/10.1016/S0140-
6736(20)30314-7]
The multicenter, two-arm, random-
ized study looked at men with biop-
sy-proven prostate cancer and high-risk
features at 10 hospitals in Australia.
[Australian New Zealand Clinical Trials
Registry ANZCTR12617000005358] Pa-
tients were randomized to undergo either
conventional CT and bone scanning or
gallium-68 PSMA-11 PET-CT. First-line
of randomization. Patients were crossed rior to conventional imaging for patients
over unless three or more distant metas- with pelvic nodal metastases and pa-
tases were identified. The study’s primary tients with distant metastases.
outcome looked at the accuracy of first-
line imaging for identifying either pelvic The study also noted that radiation
nodal or distant-metastatic diseases, exposure was higher in conventional
which is defined by the receiver-operat- imaging compared with PSMA PET-CT
ing curve using a predefined reference (19.2 mSv vs 8.4 mSv; p<0.001).
standard, and includes histopathology,
imaging and biochemistry at 6-month
follow-up.
The study found that PSMA PET-CT
had a 27 percent (95 percent CI 23–31)
greater accuracy compared to conven-
tional imaging (92 percent [88–95] vs 65
percent [60–69]; p<0.0001). Additionally,
conventional imaging was less sensitive
and specific compared to PSMA PET-CT.

Vaping and smoking potentially increases

risk of severe coronavirus infection
PANK JIT SIN York, US. [Thorax. 2018;73:1161–1169, Tarran, Ph.D, professor of cell biology

W
ith the disease being so new,
very little is known about
COVID-19 apart from the fact
that it is spreading at an alarming rate
right now. Even so, there is enough ex-
isting evidence to suggest that smok-
ers and vapers (e-cigarette users) may
possibly be negatively affected by
COVID-19. [Available at https://www.sci-
entificamerican.com/article/smoking-or-
vaping-may-increase-the-risk-of-a-se-
vere-coronavirus-infection1/. Accessed
on 30 March]
It is well established that vaping and
smoking cause inflammation of the lungs
and chronic lung conditions, said Dr
Melodi Pirzada, chief paediatric pulmo-
nologist, NYU Winthrop Hospital, New
J Immunol. 2014;192(11):5226–5235]
By extension, it is reasonable to assume
that both smoking and vaping could in-
crease the risk of developing serious in-
fection from the coronavirus.
Pirzada said this was due to the
change in defense mechanism of the
entire airway in smokers and vapers.
A study in the Chinese Medical Jour-
nal seems to back this idea. The study,
with a small sample pool of 78 patients,
revealed that those with a history of
smoking were 14 times more likely to
develop pneumonia. [doi: 10.1097/
CM9.0000000000000775]
The idea (that smokers and vapers
might be disproportionately affected by
severe COVID-19) is echoed by Robert
and physiology, University of North Car-
olina, Chapel Hill, US. He said smoking
is an established risk factor for influenza
because those who smoke are immuno-
suppressed to some degree. According
to Tarran, they also secrete more mucus,
and thus do not clear the lungs as well.
To compound matters, there are proin-
flammatory and immune cell chang-
es, all of which lead up to an increased
likelihood of getting infected and having
worse outcomes.

47
DOCTOR | APRIL ISSUE

COVID-19: Virus found in aerosols, on surfaces
for hours to days post-exposure
RACHEL SOON
S
ARS-CoV-2 may remain in aero-
sols over 3 hours after exposure,
and on surfaces up to 3 days,
making it similar to SARS-CoV-1 in en-
vironmental stability, according to a new
study.
An investigation by a team under
the US National Institute of Allergy and
Infectious Diseases (NIAID) found that
viable SARS-CoV-2 particles could
be detected in aerosols up to 3 hours
post-aerosolization, and up to 4 hours
on copper, up to 24 hours on card-
board, and up to 2-3 days on plastic
and stainless steel surfaces after expo-
sure. [medRxiv 2020; doi:10.1101/2020
.03.09.20033217]
“Our results indicate that aerosol and
fomite transmission of HCoV-19* is plau-
sible,” said the researchers.
However, study leader Neeltje van
Doremalen was careful to stress that the
study—currently in preprint and pending
peer review—did not prove anyone had
been infected by breathing aerosolized
particles or touching contaminated sur-
faces.
“Important: we experimentally gen-
erated aerosols and kept them afloat
in a drum. This is not evidence of
aerosol transmission,” said van Dore-
malen in a Twitter post on 11 March.
[https://twitter.com/DrNeeltje/sta-
tus/1237743987890343938]
The study compared one strain of
SARS-CoV-2 and one of SARS-CoV-1
at similar infectious titres under con-
trolled laboratory conditions that were
significant to healthcare settings. Aero-
sols were tested as they are produced
by certain medical procedures, while the
four surface types were those commonly
found in hospitals.
NEWSBITES
Plastic and stainless steel surfaces allow the SARS-CoV-2 virus to survive longer than cardboard and
copper surfaces.
To test viral viability in aerosols, the
researchers nebulized both strains and
maintained them using a Goldberg drum
(21–23°C, relative humidity 65 percent),
from which samples were collected by
gelatin filters after 0, 30, 60, 120, and
180 minutes.
They detected viable SARS-CoV-2
particles in aerosol up to the 180-min-
ute mark, though concentration was
reduced (infectious titre 103.5 to 102.7
TCID50/mL**). A similar reduction was
observed in the SARS-CoV-1 strain
(104.3 to 103.5 TCID50/mL).
For surface viability, 50 μl of 105
TCID50/mL of both strains were applied
to polypropylene, cardboard, stainless
steel, and copper surfaces, with sam-
ples taken after 1, 4, 8, 24, 48, 72, and
96 hours (21–23°C, relative humidity 40
percent).
On polypropylene, both viruses were
detectable up to 72 hours, though with
greatly reduced virus titre (SARS-CoV-2,
103.7 to 100.6 TCID50/mL; SARS-
CoV-1, 103.4 to 100.7 TCID50/mL). On
stainless steel, similar kinetics were ob-
served in both, though the virus was only
detectable up to 48 hours (SARS-CoV-2,
103.7 to 100.6 TCID50/mL; SARS-
48
DOCTOR | APRIL ISSUE
CoV-1, 103.6 to 100.6 TCID50/mL).
No viable virus was detectable af-
ter 4 hours on copper for SARS-CoV-2
and 8 hours for SARS-CoV-1, and after
24 hours on cardboard for SARS-CoV-2
and 8 hours for SARS-CoV-1.
At the 96-hour mark, no detectable
levels of virus were found on any of the
four surfaces.
All viability tests were repeated three
times, with results reflecting the mean
data. Decay rates were estimated using
a Bayesian regression model.
In their discussion, the researchers
noted that given how similar the environ-
mental viabilities of the two viruses were,
the greater transmissibility of SARS-
CoV-2 was likely due to other factors
such as pre-symptomatic or asymptom-
atic viral shedding, the infectious dose
needed to establish infections, and varia-
tions in temperature and humidity.
* HCoV-19: human coronavirus 19, an alternate name
for SARS-CoV-2 recently proposed over concerns
of misleading comparisons to SARS. [Lancet 2020;
doi:10.1016/S0140-6736(20)30419-0]
** TCID50: 50-percent tissue culture infective dose,
or the dose of infectious agent which induces
infection in 50 percent of a given group of tissue
cultures.
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Early exposure to cleaning products may
up risk of childhood asthma
PEARL TOH
F
requent exposure to household
cleaning products during early life
is associated with a greater risk of
childhood asthma and wheeze at age 3
years, according to the CHILD* cohort
study — adding to the growing call to
action on the risk of cleaning products
as irritants for airways of young children.
“A precautionary approach to using
cleaning products and targeted hygiene
is reasonable for housekeeping where
young children are present,” the re-
searchers highlighted.
The study followed 2,022 children
whose parents self-reported on how
often they used cleaning products in the
household when their children were aged
3–4 months. The cleaning products re-
viewed spanned across 26 categories,
including disinfectants, cleaners, bleach,
dishwashing and laundry detergents,
polishes, and air fresheners. [CMAJ
2020;doi:10.1503/cmaj.190819]
Children in homes with more frequent
use of cleaning products during early life
were more likely to have asthma at age 3
years than those with less frequent use
(adjusted odds ratio [OR], 1.37, 95 per-
cent confidence interval [CI], 1.09–1.70).
They were also more likely to devel-
op recurrent wheeze (OR, 1.35, 95 per-
cent CI, 1.11–1.64), as well as recurrent
wheeze with atopy (OR, 1.49, 95 percent
CI, 1.02–2.16), at 3 years.
When stratifying the analysis by sex,
the associations for all outcomes ap-
peared to be stronger among girls than
boys, although all were not statistically
significant.
“This is an interesting finding that
requires more research to better under-
stand male versus female biological re-
sponses to inflammatory exposures in
NEWSBITES
early life,” said principal investigator Pro-
fessor Tim Takaro of Simon Fraser Uni-
versity (SFU) in Burnaby, Canada.
Intriguingly, the risks for the respirato-
ry outcomes were greater with frequent
use of scented and sprayed products,
such as antimicrobial hand sanitizers, air
freshener sprays, plug-in deodorizers,
dusting sprays, and oven cleaners.
There was no significant association
between usage frequency of cleaning
products and atopy at age 3 years (OR,
1.14, 95 percent CI, 0.96–1.35).
“These findings add to our under-
standing of how early life exposures are
associated with the development of aller-
gic airway disease, and identify house-
hold cleaning behaviours as a potential
area for intervention,” said lead author
Jaclyn Parks, a graduate student at SFU.
According to recommendations from
the American Lung Association, air fresh-
eners should be entirely avoided and
only cleaning products that do not con-
tain volatile organic compounds, irritants,
fragrances, or flammable ingredients be
used.
“As such, removal of scented prod-
ucts from the homes of families of chil-
dren at risk of asthma, or with current
asthma symptoms, is likely wise,” wrote
Dr Elissa Abrams from University of British
47
50
DOCTOR || APRIL ISSUE
Columbia, Vancouver, Canada in a linked
commentary. [CMAJ 2020;doi:10.1503/
cmaj.200025]
“In the pursuit of obtaining a clean
and healthy home … it is important that
parents read labels and be informed
about the risks associated with the use
of cleaning products,” urged Parks and
co-authors.
Nonetheless, the findings should not
be taken as a causal relationship, cau-
tioned the researchers. Also, data on the
child’s exact location during cleaning was
unavailable, and they assumed that the
children were exposed during the process.
“It is possible that initial effects on
the airway in early life from frequent use
of cleaning products may be due to an
inflammatory rather than an acquired al-
lergic response,” suggested Parks and
co-authors on the potential mechanism
mediating the association.
“The big takeaway from this study is
that the first few months of life are critical
for the development of a baby’s immune
and respiratory systems,” said Parks.
“By identifying hazardous exposures
during infancy, preventive measures can
be taken to potentially reduce childhood
asthma and subsequent allergy risk.”
*CHILD: Canadian Healthy Infant Longitudinal
Development

Kidney function linked to glaucoma in certain
East Asian populations
ROSHINI CLAIRE ANTHONY
C
hronic kidney disease (CKD) may
be linked to primary open-angle
glaucoma (POAG) in individuals
of certain Asian ethnicities, according to
a pooled analysis of studies from Asia.
“In the overall sample, no significant
associations between kidney function and
CKD with POAG were observed. Howev-
er, significant associations were observed
in the combined subgroups of Chinese
and Koreans, suggesting that such asso-
ciation may only be present in East Asians
specifically,” said the researchers.
The researchers examined data from
nine population-based studies – com-
prising 28,925 individuals (57,340 eyes)
from China, Hong Kong, India, Korea,
Russia, and Singapore – included in the
Asian Eye Epidemiology Consortium.
Of these, 856 were determined to have
POAG (mean age 64.2 years, 50.6 per-
cent male, mean estimated glomerular fil-
tration rate [eGFR] 78.2 mL/min/1.73 m2,
18.2 percent with CKD [eGFR <60 mL/
min/1.73 m2]). They were compared with
the 28,069 individuals without POAG
(mean age 56.1 years, 45.9 percent
male, mean eGFR 86.5 mL/min/1.73 m2,
9.8 percent with CKD).
NEWSBITES
Overall, decreasing eGFR was not
associated with POAG (adjusted odds
ratio [adjOR], 1.01, 95 percent confi-
dence interval [CI], 0.96–1.05 for every
10 mL/min/1.73 m2 reduction in eGFR;
p=0.769). There was also no association
between CKD and POAG (adjOR, 1.04,
95 percent CI, 0.84–1.27; p=0.729). [Br
J Ophthalmol 2020;doi:10.1136/bjoph-
thalmol-2019-314890]
Pooled analysis found no link be-
tween reduced eGFR (β, -0.02 per 10
mL/min/1.73 m2 decrease; p=0.118) or
CKD (β, -0.04; p=0.533) with intraocular
pressure (IOP).
When assessed by individual study,
there was a significant association be-
tween reduced eGFR and POAG in the
Singapore Chinese Eye Study (OR, 1.20;
p=0.019), specifically among individuals
with diabetes (OR, 1.44; p=0.001) or
hypertension (OR, 1.21; p=0.014), while
CKD was linked to POAG in individuals
with diabetes (OR, 4.15; p=0.016). In
the Central India Eye and Medical Study,
eGFR was associated with POAG among
individuals with hypertension (OR, 1.17;
p=0.049).
In contrast to the overall findings,
subgroup analysis of Korean and Chi-
51
DOCTOR | APRIL ISSUE
nese participants (combined) showed a
significant association between reduced
eGFR and POAG (OR, 1.09 per 10 mL/
min/1.73 m2 decrease; p=0.048). Like-
wise, severe decline in kidney function,
defined as eGFR <45 mL/min/1.73 m2,
was associated with POAG (OR, 2.57;
p=0.004). Among Chinese and Korean
patients with diabetes, CKD (OR, 2.09;
p=0.032), severe decline in kidney func-
tion (OR, 4.88; p=0.002), and reduced
eGFR (OR, 1.23; p=0.003) were factors
associated with POAG.
“This finding may indicate that the
association between poorer kidney
function and POAG may be specific to
Korean and Chinese individuals,” said
the researchers, noting that this finding
could be confirmed by examining the
CKD-POAG association in the Japa-
nese population. In addition, studies
in Western populations could identify
whether ethnicity plays a role in the kid-
ney function-POAG association.
“[These findings suggest that] regu-
lar glaucoma screening among individ-
uals with kidney disease may be more
beneficial for specific East Asian ethnic-
ities, rather than wide implementation
for the whole Asian population,” they
noted.

Sprayed handrub as good as poured ones,
only if rubbing ensues
PEARL TOH
U
sing alcohol-based handrub
(ABHR) that is sprayed on the
hand is equally effective as the
one that is poured onto the hand for
disinfection, but only when both are fol-
lowed by hand rubbing, according to a
study conducted by the WHO* Collabo-
rating Centre on Patient Safety.
Applying sprayed handrub without
rubbing did not meet the noninferiority
margin for hand hygiene vs handrubbing
with ABHR poured onto the hands.
“ABHR delivered as a spray could
be an alternative method to ensure ap-
propriate hand disinfection and patient
safety as long as the correct hand rub-
bing steps are included,” the researchers
stated.
In the laboratory-based experimental
study, 19 healthcare workers (36.8 per-
cent doctors, 26.3 percent nurses; 68.4
percent female) were asked to perform
three methods of hand hygiene consist-
ing: (i) 3 mL ABHR poured onto the hand
palm followed by 30 seconds of rub-
bing, (ii) 3 mL sprayed ABHR followed
by 30 seconds of rubbing, and (iii) 3 mL
sprayed ABHR without hand rubbing.
The three methods were performed in a
randomized sequence using the same
ABHR of 60% isopropanol. [J Hosp Infect
2020;doi:10.1016/j.jhin.2020.02.008]
Hand rubbing in methods (i) and (ii)
was performed in accordance with the
6-step technique recommended by the
WHO, repeated five times; while partic-
ipants were to maintain their hands up-
right without moving for 30 seconds fol-
lowing ABHR application in method (iii).
NEWSBITES
The researchers found that hand rub-
bing with sprayed ABHR was as effective
as that performed with poured ABHR in
reducing bacterial load (mean count re-
duction, log10 3.66 CFU**/mL, 95 per-
cent confidence interval [CI], 1.68–5.64
vs log10 3.46 CFU/mL, 95 percent CI,
1.27–5.65), which met the noninferiority
margin of log10 0.6 CFU/mL as specified
by the European Norm 1500.
In fact, the reduction in bacteri-
al count appeared to be greater with
sprayed vs poured ABHR accompanied
by hand rubbing, although the difference
between groups was not statistically sig-
nificant (difference, log10 0.20 CFU/mL,
95 percent CI, -0.23 to 0.62).
In contrast, noninferiority was not
established for sprayed ABHR without
hand rubbing (mean bacterial count re-
duction, log10 2.76 CFU/mL, 95 percent
CI, 1.65–3.87).
According to the WHO guidelines,
hand hygiene should be performed using
a liquid ABHR poured onto the hand fol-
lowed by a 6-step hand rubbing tech-
nique for 20-30 seconds.
“This study has reliably shown that
hand rubbing with sprayed ABHR is non-
inferior to the current WHO recommend-
ed method of hand rubbing with the
same ABHR poured onto a hand palm,”
said the researchers.
49
52
DOCTOR || APRIL ISSUE
“Using a spray method to dispense
the ABHR could improve hand hygiene
efficacy as well as compliance,” they ex-
plained. “Spraying can uniformly deliver
ABHR to a large hand surface area within
a short period of time with minimal spill-
age, improving efficiency.”
Although the current study could not
establish noninferiority of sprayed ABHR
when hand rubbing was omitted, further
development should be encouraged,
according to the researchers. “Effective
sprays that do not require hand rubbing
could further decrease the required time
for hand hygiene, and as such increase
hand hygiene compliance.”
“Development of novel spray de-
signs, or improvements in the ABHR
formula used in sprays, could perhaps
overcome this hurdle,” they suggested.
The researchers also cautioned
that health and safety issues need to be
taken into account in developing sprayed
ABHR, as aerosols may lead to respira-
tory tract irritations, which could com-
promise hand hygiene compliance.
*WHO: World Health Organization
**CFU: Colony-forming unit

Physical activity may keep teen depression at bay
AUDREY ABELLA
A
prospective study has shown a link
between light physical activity and
a reduction in depressive symp-
toms in adolescents, suggesting that
switching from couch-potato mode to
walking even at a casual pace might help
in keeping depressive symptoms at bay.
As depression appears to start during
adolescence, this may be the ideal period
to implement strategies to curb depression
at a later stage. [Lancet 2014;383:1404–
1411; Lancet 2012;379:1056-1067]
Evidence shows that physical activity
may help reduce depressive symptoms;
however, most have focused on moder-
ate-to-vigorous activities (eg, brisk walk-
ing, jogging, cycling). [Neurosci Biobehav
Rev 2019;107:525-539]
Light activity (eg, slow walking, stand-
ing classes), which requires less effort
and is easier to integrate into a daily
routine, may be more sustainable, noted
the researchers. However, light activity is
progressively displaced by sedentary be-
haviour (ie, screen time, lying/sitting still)
throughout adolescence, as evidenced by
the current findings.
From 12 to 16 years, time spent doing
light activity decreased (mean, from 326
to 245 min/day; p<0.0001) as the duration
of sedentary behaviour increased (mean,
NEWSBITES
from 431 to 523 min/day; p<0.0001).
[Lancet Psychiatry 2020;7:262-271]
A 60-minute/day exposure to seden-
tary behaviour between 12 and 16 years
led to depression rates ranging from
8–11 percent at 18 years, with the stron-
gest association observed at 12 years
(incidence rate ratio, 1.11; p<0.0001).
Correspondingly, every 60-minute/day
light activity during the same timepoints
led to a drop in depression rates by 8–11
percent.
These results reflect the consistent
association between increased seden-
tary behaviour throughout adolescence
and depressive symptoms at 18 years,
said the researchers. “[These imply] that
a 2-hour reduction in daily sedentary be-
haviour between … 12 and 16 years was
associated with a 16–22-percent reduc-
tion in depression scores by 18 years. For
young people with subclinical depressive
symptoms, a reduction of this magnitude
can have a substantial impact.”
These were observed following eval-
uation of a subsample of adolescents
(n=4,257, 56 percent female) from the
ALSPAC* study who had a CIS-R** de-
pression score at 18 years. The amounts
of time spent in sedentary behaviour and
physical activity were measured using
accelerometers at 12, 14, and 16 years.
Participants were followed for 6 years.
53
DOCTOR | APRIL ISSUE
Drop the remote
Evidence shows that mentally active
sedentary behaviours (eg, working at a
desk) may also lower the risk of depres-
sive symptoms than mentally passive
sedentary behaviours (eg, watching TV).
[Br J Psychiatry 2019;1-7] Nonetheless,
the study findings highlight the impor-
tance of light movement to mitigate the
potential dangers of globally rising sed-
entary behaviour in young people, said
the researchers.
Therefore, public health guidelines
and interventional approaches should
include measurable and achievable tar-
gets for promoting light activity to dis-
place sedentary behaviour and potential-
ly pull the adolescent depression curve
down, they said. “[I]ndividual, school, or
community levels [should] incorporate
extended bouts of light activity into the
daily routines of young people, such as
standing lessons, increasing active trav-
el time between classes, or promoting
lightly active hobbies such as playing an
instrument and painting.”
However, the researchers noted that
attrition over time could have resulted
in selection bias. There may have also
been some degree of inaccuracy with
accelerometer use (eg, inability to re-
cord posture), they added. Nonethe-
less, the long follow-up period, large
patient sample, and repeated objective
measures fortified the groundwork for
the robust findings.
“[Overall,] emphasizing the men-
tal health benefits of physical activity
would send a stronger and more relat-
able message given the rising prevalence
of depression in adolescents,” said the
researchers. Future studies should also
explore the impact of physical activity
and sedentary behaviour on other mental
health issues such as anxiety disorders.
*ALSPAC: Avon Longitudinal Study of Parents And
Children
**CIS-R: Clinical Interview Schedule-Revised

Nocturia more bothersome for young
people than adults
TRISTAN MANALAC
Y
ounger people also suffer from
nocturia and are more bothered
by it than older adults, according
to a new study.
“To our knowledge, this is the first
study exploring and describing the point
prevalence of nocturia in a nonpatient
population using data collected directly
by wearable devices and from User-Re-
ported-Outcomes gathered through
software associated with the wearables,”
the researchers said.
The study included a retrospective
cohort (n=250,000, 57 percent male),
from whom wearable device sleep data
were retrieved. This group logged a mean
443 minutes of total sleep, with sleep effi-
ciency declining with time. A prospective
cohort of 6,230 participants (mean age
47.4 years, 59.5 percent male) was also
included and made to complete a survey.
[Int J Clin Pract 2020;26:doi:10.1111/
ijcp.13495s]
Of the overall sample, 14.2 percent
reported getting up to urinate twice or
thrice or more times per night. This be-
came more common with age, with a
prevalence of 4.1 percent in patients
aged 18–24 years as opposed to 49.1
percent in the 75–90-year age group.
NEWSBITES
Nocturia was also more common in
women under the age of 65 and in men
older than the age of 65.
The level of bother also intensified
with the level of nocturia. For instance,
55.3 percent of respondents who need-
ed to get up at least thrice per night to
void reported that they were “quite a bit”
or “extremely” bothered by it. The fre-
quency of this sentiment dropped to 37.4
percent in participants with two nightly
voids, and to 23.2 percent in those with
zero to one void.
The effects of these sleep distur-
bances also extended into the daytime.
A higher proportion of patients with at
least three night-time voids reported
that their daytime activities “quite a bit”
or “extremely” affected, relative to those
with two, or fewer, voids (20.1 percent vs
11.0 percent vs 3.3 percent).
Notably, disaggregation according to
age showed that younger respondents
were more bothered by nocturia. At three
or more voids per night, 55.6 percent
and 62.7 percent of participants aged
18–44 and 45–64 years, respectively, re-
54
DOCTOR | APRIL ISSUE
ported high levels of bother at night. In
comparison, the same was true for less
than half of those aged 65–90 years.
In turn, daytime bother at three or
more voids per night was greater in re-
spondents aged 18–44 vs those aged
65–90 years (27.8 percent vs 14.1 per-
cent).
“This study demonstrated the fea-
sibility of using data from wearables to
study the association between nocturia
and sleep,” the researchers said.
“Leveraging the power of wearables
and the associated digital communica-
tion channels to perform remote diag-
nosis as well as increase medical literacy
and awareness on possible conditions
one may suffer from, in a two-way com-
munication model, especially in a young
population, could have remarkable ben-
eficial effects,” they added. “To what ex-
tent such interventions may contribute to
quality of care improvement remains an
important area for future research.”

Different foods have varying effects
on stroke subtypes
ROSHINI CLAIRE ANTHONY
C
onsumption of certain foods may
affect the risk of ischaemic or
haemorrhagic stroke, with dif-
ferent foods implicated in the different
stroke subtypes, a European study has
shown.
“The most important finding is that
higher consumption of both dietary fibre
and fruit and vegetables was strongly
associated with lower risks of ischaemic
stroke, which supports current European
guidelines,” said first author Dr Tammy
Tong from the Nuffield Department of
Population Health, University of Oxford,
Oxford, UK.
“The general public should be recom-
mended to increase their fibre and fruit
and vegetable consumption, if they are
not already meeting these guidelines.”
Tong and co-authors examined
data of 418,329 individuals from nine
European countries (the EPIC* cohort).
Country-specific questionnaires were
deployed to assess dietary intake over
the year pre-enrolment. Over the mean
12.7-year follow-up period, 4,281 cases
of ischaemic stroke and 1,430 cases of
haemorrhagic stroke were documented.
A higher consumption of fruits and
vegetables was associated with a lower
risk of ischaemic stroke (adjusted haz-
ard ratio [adjHR], 0.87 per 200 g/day,
95 percent confidence interval [CI],
0.82–0.93; ptrend<0.001). [Eur Heart J
2020;doi:10.1093/eurheartj/ehaa007]
Other foods associated with a re-
duced risk of ischaemic stroke were di-
etary fibre (adjHR, 0.77 per 10 g/day, 95
percent CI, 0.69–0.86; ptrend<0.001) and
dairy (milk: adjHR, 0.95 per 200 g/day,
95 percent CI, 0.91–0.99; ptrend=0.02;
cheese: adjHR, 0.88 per 30 g/day, 95
percent CI, 0.81–0.97; ptrend=0.008; yo-
ghurt: adjHR, 0.91 per 100 g/day, 95
NEWSBITES
percent CI, 0.85–0.97; ptrend=0.004).
Conversely, a higher intake of red meat
showed a trend toward increased risk of
ischaemic stroke (adjHR, 1.07 per 50 g/
day; ptrend=0.20).
For haemorrhagic stroke, a higher in-
take of eggs was linked to an increased
risk (adjHR, 1.25 per 20 g/day, 95 per-
cent CI, 1.09–1.43; ptrend=0.002).
According to the authors, the associ-
ations may at least be partially explained
by the effects of the foods on blood pres-
sure (BP) and cholesterol. For example,
in this study, higher egg consumption
was linked to a slightly elevated systolic
BP, while fibre was associated with re-
duced non-HDL-cholesterol levels, they
said.
The authors noted the lack of asso-
ciation between fish intake and stroke,
which contrasts with findings of previous
meta-analyses that showed an inverse
association between fish intake and both
stroke subtypes. [BMJ 2012;345:e6698;
Eur J Clin Nutr 2012;66:1199-1207]
Tong and co-authors put this down to
between-study heterogeneity in the me-
ta-analyses which included variations
with fish type, location, and preparation
55
DOCTOR | APRIL ISSUE
methods. In addition, the lack of asso-
ciation between legume or nut intake
with stroke risk could be due to low
consumption of these foods among the
study population, they said.
In terms of dietary association with
stroke, previous research has large-
ly looked at stroke risk as a whole and
not broken down into subtypes, said
the researchers. [Crit Rev Food Sci Nutr
2019;59:1071-1090]
“Our study also highlights the impor-
tance of examining stroke subtypes sep-
arately, as the dietary associations differ
for ischaemic and haemorrhagic stroke,
and is consistent with other evidence,
which shows that other risk factors, such
as cholesterol levels or obesity, also influ-
ence the two stroke subtypes differently,”
said Tong.
The observational study design pre-
vents determination of causality, and the
primarily Caucasian population limits the
generalizability of the findings, the au-
thors noted. Lack of data on medication
use and the single assessment of dietary
intake were also limitations.
*EPIC: European Prospective Investigation into Cancer
and Nutrition

Gluten contact in kids with coeliac disease:
Hygiene is key
AUDREY ABELLA
A
quantitative assessment showed
that gluten cross-contact in
school environments may pose a
concern for children with coeliac disease
(CD), underscoring hygiene practices to
mitigate the risk of gluten transfer.
As CD rates in children continue to
increase, learning facilities are faced
with the challenge of meeting their
gluten-free (GF) demands. [Avicen-
na J Med 2017;7:171-175] Contact
with gluten, which is inherent in some
school supplies, could instigate fear
and anxiety in parents of children with
CD, leading to hypervigilance and de-
creased quality of life. [J Pediatr Gas-
troenterol Nutr 2018;66:58-63; J Pedi-
atr Nurs 2015;30:353-363; Dig Dis Sci
2018;63:1438-1448]
“[T]ouching any gluten-containing
school supplies … can be challeng-
ing, especially for young children,” said
study author Vanessa Weisbrod from the
Children’s National Hospital in Washing-
ton, DC, US, in a press release. “Under-
standing how children may be exposed
to gluten within the school environment
and how this may be mitigated would
facilitate safe participation [in learning
activities for children with GF needs].”
Thirty children (50 percent female,
median age 8 years) without CD or gluten
intolerance participated in five, 5-minute
sensory play activities. All kids partici-
pated in the modelling clay and baking
project activities, while 10 kids joined the
paper mâché and dry and cooked pasta
experiments. Kids were then instructed
to clean hands using either soap and
water, water alone, or wet wipes. Glu-
ten transfer was measured through GF
bread rubbed on the kids’ hands and
table surfaces after activity. Efficacy of
cleaning methods was measured from
different bread samples rubbed post
washing (modelling clay and baking proj-
NEWSBITES
ect participants only). [J Pediatr Gastro-
enterol Nutr 2020;70:289-294]
All post-activity bread samples from
modelling clay and dry pasta users re-
vealed a negligible amount of gluten trans-
fer (<20 ppm), with almost all dry pasta
arm samples (n=9) having undetectable
gluten levels (<5 ppm). Conversely, the
paper mâché, cooked pasta, and bak-
ing project activities led to gluten transfer
rates that were far greater than the 20-
ppm threshold*, with most samples ex-
ceeding the upper limit of >84 ppm.
“These findings make an easy distinc-
tion – dry and non-sticky [supplies] show
very low gluten transfer while … wet and
pasty ones cling heavily to hands and
table surfaces [thus] posing a higher risk
of gluten exposure,” said Weisbrod.
These results underline the impor-
tance of having GF supplies in schools or
devising a strategy (eg, substitution) for
gluten cross-contact prevention, noted
the researchers. For instance, the white
flour in traditional paper mâché may be
replaced by rice flour or corn starch.
Corn- and rice-based pastas, which are
now increasingly available, may substi-
tute gluten-containing ones.
Wash, wash, wash
Regardless of handwashing method,
gluten levels in all post-washing bread
samples in the modelling clay arm were <5
ppm. The levels were also undetectable in
63 percent of samples in the baking proj-
ect arm, with the soap-and-water tandem
reigning supreme for gluten removal.
“Whether you’re protecting from bac-
teria or gluten, handwashing and surface
hygiene are key … [T]his study shows
that the number one thing we can do is
teach our kids to wash their hands,” said
Weisbrod.
The risk of ingestion also highlights
the importance of sanitation, noted the
56
DOCTOR | APRIL ISSUE
researchers. “[Handwashing] should be
required … following [activity], and work-
spaces should be cleaned to prevent
transfer, especially if food will be con-
sumed later in the same space.”
Co-author Dr Amy Damast from
Temple Sinai in Summit, New Jersey, US
said that the study is a “win” for both stu-
dents and their schools. “[Our] findings
should reassure us [that] all routine, care-
ful handwashing and surface-cleaning
methods will keep children with CD safe
and healthy while allowing them to par-
ticipate in more activities that may involve
gluten-containing materials.”
The educational, social,
emotional toll
Evidence has shown that untreated
CD may impact school performance,
ranging from lack of focus to absen-
teeism, subsequently leading to lower
educational attainment. [J Pediatr Gas-
troenterol Nutr 2019;69:690-695; Arch
Dis Child 2018;103:143-148; Scand J
Gastroenterol 2005; 40:1407-1412]
Moreover, children aware of their
plight are often compelled to refuse
social invitations, noted the research-
ers. “[They] report feeling left out and
different from their peers because they
had to eat something they brought from
home or had to say no … They often
feel isolated.”
Therefore, effective management
should consider the social and emotional
impact of CD on children. Parents of kids
with CD are encouraged to work closely
with the appropriate school authorities,
noted the researchers. A combined effort
will help foster an environment that suits
the needs of children with CD so they
may fully immerse in all activities instru-
mental for learning, social, and emotional
development, they added.
*as per Codex Alimentarius Commission

Inclisiran lowers LDL
levels in patients at
high risk for ASCVD
ELAINE SOLIVEN
T
reatment with inclisiran led to a
significantly reduced low-density
lipoprotein (LDL) cholesterol levels
in patients with atherosclerotic cardio-
vascular disease (ASCVD), according to
two phase III randomized clinical trials.
The ORION-10* and ORION-11**
cohorts consisted of 1,561 and 1,617
patients aged 65–66 years (mean LDL,
104.7 and 105.5 mg/dL, respectively)
with ASCVD or ASCVD risk equivalent
who had elevated LDL cholesterol levels
and were previously treated with statin
at a maximum tolerated dose. Partici-
pants were randomized in a 1:1 ratio to
receive either four subcutaneous injec-
tions of inclisiran 284 mg or placebo on
day 1 and 90, and subsequently every 6
months for a 540-day treatment period.
[N Engl J Med 2020;doi:10.1056/NEJ-
Moa1912387]
Inclisiran-treated patients had sig-
nificantly reduced LDL cholesterol lev-
els compared with the placebo-treated
patients at day 510 in ORION-10 (ab-
solute change, -56.2 vs -2.1 mg/dL;
between-group difference, -52.3 per-
cent; p<0.00) and ORION-11 trials (ab-
solute change, -50.9 vs 1.0 mg/dL; be-
tween-group difference, -49.9 percent;
p<0.001).
Both trials also demonstrated sig-
nificantly lower time-adjusted change in
LDL cholesterol levels in patients who re-
ceived inclisiran vs placebo at day 90 and
until day 540 (absolute change, -53.7 vs
-0.4 mg/dL; between-group difference,
-53.8 percent; p<0.001 in ORION-10
and absolute change, -48.6 vs 0.3 mg/
dL; between-group difference, -49.9 per-
cent; p<0.001 in ORION-11).
Among all the participants, PCSK9***
levels decreased by 69.8 percent and
NEWSBITES
63.5 percent (p<0.001 for both) in the in-
clisiran arm, whereas increased PCSK9
levels were observed in the placebo
arm at 13.5 percent and 15.6 percent
(p<0.001 for both) in the ORION-10 and
ORION-11 trials, respectively. “Inclisiran,
a small interfering RNA (siRNA) therapeu-
tic agent, reduces hepatic synthesis of
PCSK9,” the researchers said.
In a prespecified exploratory analysis,
the cardiovascular composite outcome
occurred at a lower rate of 7.4 percent
and 7.8 percent in the inclisiran arm com-
pared with 10.2 percent and 10.3 per-
cent in the placebo arm for both ORION-
10 and ORION-11 trials, respectively.
The incidence of adverse events
(AEs) were comparable between the in-
clisiran and placebo arms (73.5 percent
vs 74.8 percent [in ORION-10] and 82.7
percent vs 81.5 percent [in ORION-11]).
However, injection-site AEs occurred
more frequently in the inclisiran arm than
the placebo arm for both trials (2.6 per-
cent vs 0.9 percent [in ORION-10] and
4.7 percent vs 0.5 percent [in ORION-
11]), which were mostly mild or moderate
54
57
DOCTOR || APRIL ISSUE
in severity. “[Of note, even] without fur-
ther injections, the LDL cholesterol-low-
ering effects of inclisiran are reversed at
the rate of approximately 2 percent per
month, which means that these effects
can persist for up to approximately 2
years,” the researchers noted.
Although more injection-site AEs
were reported in the inclisiran group, “we
found that a regimen of inclisiran every 6
months was feasible and significantly re-
duced LDL cholesterol levels by approxi-
mately 50 percent,” said the researchers,
noting that “sustained reductions in LDL
cholesterol levels are achievable [even]
with an infrequent dosing schedule of
inclisiran.”
“[Furthermore,] the results of our
trials have the potential to move RNAi-
based therapies from the realm of rare to
common diseases,” they added.
*ORION-10: Inclisiran for participants with atheroscle-
rotic cardiovascular disease and elevated low-density
lipoprotein cholesterol
**ORION-11: Inclisiran for subjects with ACSVD or
ACSVD-risk equivalents and elevated low-density
lipoprotein cholesterol
***PCSK9: Proprotein convertase subtilisin-kexin
type 9
 RESEARCH REVIEWS
Baricitinib gets
breakthrough
therapy tag for
alopecia areata
T
he US Food and Drug Administration (FDA) has grant-
ed breakthrough therapy designation (BTD) to barici-
tinib for the autoimmune disorder alopecia areata.
BTD is meant to expedite the development and review
of treatments that offer a substantial improvement for a seri-
ous disease compared with existing therapies.
Alopecia areata can cause unpredictable hair loss and
currently there are no FDA-approved therapies for this con-
dition.
The BTD tag is based on the results of the BRAVE-AA1
study, which evaluated baricitinib vs placebo in adult pa-
tients. The phase 2 portion of the study showed no safe-
ty signals or serious adverse events with the drug after 36
weeks of treatment. The results allowed a phase 3 study
(BRAVE-AA1) and a late-stage clinical trial (BRAVE-AA2) to
look into the efficacy and safety of 2 mL and 4 mL doses of
baricitinib relative to placebo.
Baricitinib is an oral Janus kinase inhibitor FDA-ap-
proved for the treatment of adults with moderate-to-severe
rheumatoid arthritis who have not responded adequately to
one or more tumour necrosis factor (TNF) inhibitor thera-
pies.
https://fda.einnews.com/search/baricitinib/?search%5B%5D=
news&search%5B%5D=press&search%5B%5D=events&search%5B%5D=
fragments&order=relevance
58
DOCTOR | APRIL ISSUE
EMA suspends use
of ulipristal acetate
for fibroids pending
review
W
omen should stop using 5-mg ulipristal acetate
for uterine fibroids while a review of liver injury risk
is ongoing, says the European Medicines Agen-
cy’s (EMA) Pharmacovigilance Risk Assessment Commit-
tee.
“No new patients should start treatment with the medi-
cines, which will be temporarily suspended throughout the
EU [European Union] during the review,” said the EMA in a
statement.
The review was called for following a recent case of liver
injury that prompted a liver transplantation in a woman tak-
ing ulipristal acetate.
It can be recalled that the EMA had announced a liver
safety review of ulipristal acetate in early December 2017.
In early February 2018, the agency concluded the review
and said there is a risk for rare but serious liver injury with
the drug, but measures were implemented to minimize the
risk. A new review is ongoing following the new case report.
The EMA also advised doctors with patients currently on
the drug to immediately report signs and symptoms of liver
injury (nausea, vomiting, right hypochondrial pain, anorexia,
asthenia, and jaundice).
The EMA said recommendations regarding ulipristal ac-
etate for uterine fibroids will be provided once the review is
concluded. It also clarified there are no liver injury concerns
with the single-dose ulipristal acetate emergency contracep-
tive.
https://www.ema.europa.eu/
en/medicines/human/referrals/
ulipristal-acetate-5mg-medicinal-
products

PEARL TOH
A
novel, wearable heart fail-
ure (HF) patch accurately
predicted worsening HF
and impending rehospitalization
days before the event actually
happened in adults who were re-
cently discharged from hospital-
ization for HF (HHF), according to
the LINK-HF* study.
With a predictive accuracy
that was comparable to implanted
devices, the wearable sensor thus
presents a low-cost noninvasive
approach to reducing HHF.
“Because not all HF patients
have an indication for a pacemaker
or a defibrillator, and because im-
CLINICAL INSIGHTS | DEVICE
Wearable sensor patch
reliably predicts worsening
heart failure
plantation of a dedicated device presents
procedural risks, noninvasive methods
of monitoring may be more useful and
cost-effective in patients temporarily at in-
creased risk of HF-related hospitalization,”
the investigators said.
The multicentre, observational study
involved 100 participants (mean 68.4
years, 98 percent male) who were hos-
pitalized for an acute HF exacerbation.
After hospital discharge, they were
asked to wear the sensor patch on the
chest 24 hours a day, for at least 30
days and up to 90 days. [Circ Heart Fail
2020;13:e006513]
“We have shown that
we can predict the
future. Next, we will
look at whether we can
change the future”
Continuous streams of incoming data
of vital signs such as respiratory rate,
heart rate, heart rhythm, and physical
activities (including body posture, walk-
ing, and sleeping) for each participant
were subjected to a machine learning al-
gorithm to derive a personalized baseline
model of what is considered as “normal”
physiological values for each patient. Any
deviation from the expected “normal”
baseline value will trigger an alert to indi-
cate a worsening of HF.
During the study, 35 unplanned non-
trauma hospitalization events had oc-
curred, of which 24 events were due to
worsening HF.
The sensor platform was able to pre-
dict the risk of HHF with 76.0–88.5 per-
cent sensitivity, which the investigators
noted, was comparable with implanted
59
DOCTOR | APRIL ISSUE
devices. Specificity of the sensor plat-
form was 85 percent.
Moreover, the sensor was able to
alert patients of an impending worsening
HF at a median of 6.5 days (interquartile
range, 4.2–13.7) before they were actu-
ally readmitted to hospital. According to
the authors, the length of the interval is a
time window that should allow for inter-
vention to be introduced to reverse the
worsening.
“With the use of remote data from the
sensor, … we have shown that we can
predict the future. Next, we will look at
whether we can change the future,” said
lead author Professor Josef Stehlik, the
University of Utah School of Medicine in
Salt Lake City, Utah, US. “With the evolu-
tion of technology and with artificial intel-
ligence statistical methods, we have new
tools to make this happen.”
“The risk of hospitalization is signifi-
cantly elevated in the first 90 days after
hospital discharge ... This time of in-
creased risk, therefore, appears to be an
opportune period for noninvasive moni-
toring aimed at identifying patients with
incipient HF decompensation,” suggest-
ed Stehlik and co-authors.
As the study population comprised
mostly men with HFrEF**, it remains un-
known if similar findings also apply to fe-
male patients and those with HFpEF***.
“A critical step will be implementation
into clinical workflow and development
of an algorithmic treatment response to
system clinical alerts,” the investigators
stated.
* LINK-HF: Multisensor noninvasive remote
monitoring for prediction of HF exacerbation
** HFrEF: HF with reduced ejection fraction
 CLINICAL INSIGHTS | IN PRACTICE
Managing insomnia in primary care
A
population survey conducted in
Singapore in 2002 among 430
individuals aged 18–64 years
showed that almost half the population
(n=200) reported sleeping difficulties.
[Singapore Med J 2015;56:317-323] An
Dr Poon Shi Hui international survey of 10,132 individu-
als from Japan, France, Germany, Italy,
Spain, the UK, and the US found that
Dr Poon Shi Hui, the rate of sleeping problems was 56
a consultant at percent in the US, 31 percent in Western
the Department of Europe, and 23 percent in Japan. [Curr
Med Res Opin 2008;24:307-317]
Psychiatry at Singapore
General Hospital, Causes and risk factors
speaks to Roshini Claire There are multiple causes or risk factors
Anthony on the different for insomnia. Common ones include
types of insomnia psychiatric disorders (eg, depression,
anxiety, substance use disorder, or
and the various
post-traumatic stress disorder) and other
management strategies sleep disorders (eg, sleep apnoea, rest-
deployed for each type. less leg syndrome).
Poor sleep hygiene, certain medica-
tions or stimulants (eg, caffeine, methyl-
phenidate, theophylline, antidepressants,
beta blockers, glucocorticoids), and
stress can also lead to insomnia, as can
medical problems such as pulmonary
disease (eg, difficulty breathing, pooling
of secretions), cancer, and chronic pain.
Intrinsic factors and genetics can
also play a role, with a higher risk among
females, especially during the peri- and
postmenopausal periods, those of older
age, individuals with a personal or family
history of insomnia, and those with a pre-
disposition toward being more aroused
from sleep.
Diagnosing insomnia
Insomnia is diagnosed through a clinical
evaluation which comprises a detailed
history taking of medical, psychiatric, and
sleep history, and accounting for predis-
posing and precipitating factors that may
be relevant when insomnia began such
as social, medical, or psychiatric events,
and stress.
60
DOCTOR | APRIL ISSUE
This is important as insomnia due to
pain, shortness of breath, or other medi-
cal conditions is unlikely to improve with-
out maximal treatment of the underlying
medical disorder. This is also the case
for sleep disorders other than insomnia
(eg, obstructive sleep apnoea, restless
leg syndrome) which may present with
insomnia but are unlikely to improve
without treatment of the specific sleep
disorder.
Perpetuating factors such as be-
havioural or cognitive responses to
sleeplessness that may be maladaptive
(eg, poor sleep habits, unrealistic expec-
tations of sleep) need to be identified,
as do circadian rhythm disruptions that
potentially complicate the clinical picture.
Overnight polysomnography (PSG)
is a standard tool used to evaluate
sleep-related pathophysiology. It is the
most objective diagnostic measure but is
not routinely used.
It is important that GPs differentiate
between acute and chronic insomnia.
Acute insomnia is the more common of
the two. It lasts less than 1 month and
usually has an immediate precipitant
such as a recent psychological or physi-
ological stressor. Individuals with chronic
insomnia have episodes at least 3 times
a week, with the condition recurring for
≥3 months.
It is also a challenge to differentiate
between primary insomnia, which has no
underlying cause, and secondary insom-
nia which has an underlying cause.
Treating insomnia
If the patient has secondary insomnia,
the cause of insomnia would be treated
as the primary condition.
For primary insomnia, treatment
measures differ according to whether the
insomnia is acute or chronic.

For acute insomnia, discussion of the
role of stressors can provide control or
acceptance of sleeplessness. If the con-
dition is severe or is due to substantial
stress, short-term use of sedative med-
ications may be helpful. This includes
short- or intermediate-acting benzodiaz-
epines for 2–4 weeks to address daytime
sleepiness and control anxiety about
sleep. The goal of this treatment mea-
sure is to minimize additional psycholog-
ical and physical stress that is produced
by insomnia. It also reduces the devel-
opment of dysfunctional cognitive and
behavioural responses to sleeplessness
which could predispose to chronic in-
somnia. These medications are effective
and well tolerated for short-term use.
A follow-up assessment after 2–4
weeks will help the GP re-evaluate the
patient’s condition and decide whether to
refer the patient for cognitive behavioural
therapy for insomnia (CBT-I).
For chronic insomnia, CBT-I and
medications are the mainstay of treat-
ment. However, CBT-I in the first-line set-
ting* may not be effective or accessible to
all patients, while some patients may pre-
fer long-term use of medications which is
also an acceptable measure. If rapid re-
sponse is needed for clinical reasons (eg,
deterioration in daytime function or ex-
cessive anxiety regarding sleeplessness),
CLINICAL INSIGHTS | IN PRACTICE
which may affect the patient’s ability to A major challenge to treatment is
follow sleep restrictions and CBT-I, medi- that patients often desire a ‘quick fix’ or
cations can be tapered over time. in some cases, develop a psychological
and physiological dependence on certain
Short-term trials have shown that medications.
CBT-I alone and CBT-I with medications
demonstrate relatively equivalent out- Conclusion
comes, and both strategies are superior Insomnia is a very common disorder
to medications alone, which was also and can be the presenting symptom
the case in longer term studies lasting for various conditions. It is important to
between 12 and 24 months. CBT-I with- take a thorough history and revisit diag-
out medication has the advantage of not nosis if treatment options don’t work.
exposing patients to side effects and po- GPs should educate patients on sleep
tential drug interactions. However, there hygiene as a preventive measure. They
is no predictor of treatment response to should also ensure that other causes of
CBT-I or medications. If a patient does insomnia are ruled out, assess the pa-
not respond to treatment, the physician tient’s medications to avoid worsening of
needs to take a thorough history, per- their insomnia, reinforce sleep hygiene,
form PSG if clinically indicated, and re- start first-line treatment, and refer the pa-
visit the diagnosis. tient to a specialist, if necessary.
Psychiatric disorders and insomnia
have a bidirectional relationship, and * CBT-I in the first-line setting as endorsed in
concomitant treatment is vital to hasten the clinical practice guidelines of the American
Academy of Sleep Medicine, British Association
recovery and induce a sustained re- for Psychopharmacology, American College of
sponse. Physicians, and European Sleep Research Society.
Practice guidelines
There are no local guidelines on the management of insomnia.
GPs can refer to the guidelines published by the American Academy of Sleep
Medicine (https://aasm.org/clinical-resources/practice-standards/).
Information provided by the National Sleep Foundation may also be useful
(https://www.sleepfoundation.org/).
61
DOCTOR | APRIL ISSUE
 HUMOUR

“See those dark spots in your lungs? “I don’t know why I don’t care about
I accidentally spilled coffee over the X-ray!” your clinomania, but I don’t!”

“I guess it’s not just a benign prostatic “Thanks, no more for me, Joe. I’m making an effort
hyperplasia, after all!” to limit my dependency on liver transplants!”

“An eagle came straight through the ceiling and “Sorry, Mr Fernet. I should have inquired as to the
grabbed the patient!” kind of surgery you needed before I operated on you!”

63
DOCTOR | APRIL ISSUE

APRIL
18-19
SATURDAY–SUNDAY
PMPASKL 60th Annual Scientific
Congress 2020
Location: Eastin Hotel, Petaling Jaya
Tel: (03) 8996 0700/1700/2700
Fax: (03) 8996 4700
Email: secretariat@acadmed.my
Postponed to October 24-25
APRIL–MAY
25-1
SATURDAY–FRIDAY
American Academy of
Neurology (AAN) Annual Meeting
Location: Toronto, Ontario, Canada
Tel: 800 879 1960; 612 928 6000
(international)
Fax: 612 454 2746
Email: memberservices@aan.com
Website: www.aan.com/
conferencescommunity/annual-meeting
MAY
30
SATURDAY
Hong Kong Academy of
Medicine (HKAM) Medical
Education Conference 2020
Location: HKAM Jockey Club Building,
Hong Kong
Email: mec2020@event.hkam.org.hk
Website: https://online.
hkam.org.hk/form/mec2020/
CALENDAR
APRIL
23-25
THURSDAY–SATURDAY
World Allergy Organization
International Scientific
Conference (WISC)
Location: Rome, Italy
Email: waoromeconference@biomedia.net
Website: www.worldallergy.org/wisc2020
Postponed to July 16-18
MAY
13-16
WEDNESDAY–SATURDAY
Society for Cardiovascular
Angiography and Interventions
(SCAI) Scientific Session
Location: Atlanta, Georgia, US
Tel: 202 741 9854; 800 992 7224
Fax: 202 689 7224
Email: info@scai.org
Website: www.scai.org/scai2020
JULY
16-19
THURSDAY–SUNDAY
Malaysian Thoracic Society 2020
Congress
Location: Fraser Place, Johor
Email: m.thoracicsociety@gmail.com
Website: https://2020.mts.org.my/
64
DOCTOR | APRIL ISSUE
APRIL
24-29
FRIDAY–WEDNESDAY
American Association
for Cancer Research (AACR)
Annual Meeting
Location: San Diego, California, US
Tel: 215 440 9300
Email: aacr@aacr.org
Website: www.aacr.org/Meetings/Pages/
MeetingDetail.aspx?EventItemID=213
Virtual participation on April 27-28
MAY
15-20
FRIDAY–WEDNESDAY
American Thoracic Society (ATS)
International Conference
Location: Philadelphia, Pennsylvania, US
Tel: 1 212 315 8600
Fax: 1 212 315 6498
Email: conference@thoracic.org
Website: https://conference.thoracic.org
JULY
23-26
THURSDAY–SUNDAY
Malaysian Society of
Anaesthesiologists & College
of Anaesthesiologists, AMM
Annual Scientific Congress 2020
Location: Shangri-La Hotel, Kuala Lumpur
Tel: (03) 8996 0700/1700/2700
Website: http://www.msa.asm.org.my/
Email: secretariat@msa.asm.org.my