MIMS Doctor November 2017 ID PDF

YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA INDONESIA NOVEMBER 2017
Managing diabetes
in primary care Statins
Highlights from slash long-term
AFOS & APCH
APDW & EASD
death risk
in men without
CVD
CONTENTS
MIMS DOCTOR - YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA Managing Editor
Elvira Manzano
Contributing Editors
Roshini Claire Anthony, Pearl Toh,
Stephen Padilla, Jairia dela Cruz,
Elaine Soliven, Audrey Abella,
Christina Lau, Jackey Suen,
NOVEMBER ISSUE Dr Joseph Delano Fule Robles
Designer
Peggy Tio
Cover Story
6 Statins slash long-term death risk in men without CVD Production
Tetsuya Hamaki, Ho Wai Hung,
Agnes Chieng
Conference Coverage
Asian Federation of Osteoporosis Societies (AFOS 2017) 5th Annual Scientific Circulation Executive
Christine Chok
Meeting, Kuala Lumpur, Malaysia
8 Genetic advances in osteoporosis: What’s next? Accounting Manager
Minty Kwan
9 Drug holiday for osteoporosis: Who, when, how long? Advertising Coordinator
Raymond Choo
10 Best practices in assessing BMD
CEO
Yasunobu Sakai
12 Treatment failure in osteoporosis: What can be done?
CMO
Sherlynn Tan
13 1 in 4 men has osteoporosis, yet most underdiagnosed
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CONTENTS
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4
COVER STORY
Statins slash long-term

death risk in men without
CVD
6
COVER STORY
PEARL TOH Compared with pravastatin-treated ject – to residual confounding, includ-
P
participants with LDL-C <190 mg/dL, ing the lack of continuing information
rimary-prevention statins were those with LDL-C ≥190 mg/dL derived on medication use. Also, the study
associated with a 28 percent more than twice the benefit of pravas- population comprised a large propor-
reduction in long-term risk of tatin in terms of an absolute risk re- tion of smokers (at least 40 percent in
death from coronary heart disease duction (ARR) in deaths from CHD, CV each group), which according to the in-
(CHD) in men with very high LDL-C causes, or any cause (ARR, 2.34, 3.25, vestigators “might mean that a similar
levels (≥190 mg/dL) and without es- and 5.39 percent, respectively). study today might not show as strong
tablished heart disease at baseline, an effect with a statin regimen of similar
according to a post hoc analysis of the Diving deeper into potency.”
WOSCOPS* trial. long-term data
Among participants with LDL-C Added value for clinical
“The present analysis provides ≥190 mg/dL, achieving a >30 percent practice
novel supporting evidence from a (39 mg/dL) reduction in LDL-C with While the ACC/AHA** cholesterol
randomized trial to reinforce current pravastatin was associated with lower guidelines recommend that individuals
recommendations of initiation of lip- risks of developing CHD and MACE with LDL-C ≥190 mg/dL be treated
id-lowering therapy in the primary pre- than those in the placebo group. Par- with high-intensity statin therapy, ran-
vention of individuals with primary ele- ticipants whose LDL-C reduction with domized trial evidence for statins were
vations of LDL-C ≥190 mg/dL without pravastatin was <30 percent did not lacking for those with very high LDL-C
the need for risk estimation,” wrote differ from placebo controls in their risks but without pre-existing vascular dis-
the investigators. of CHD and MACE. ease.
The post hoc analysis on Based on a CV disease risk calcu- “[W]e show that statins reduce
WOSCOPS includes data collected lator, a majority (67 percent) of the trial the risk of death in this specific group
during the randomized-trial phase and participants with LDL-C ≥190 mg/dL of people who appear largely healthy
observational post-trial follow-up of who were free from diabetes had a 10- except for very high LDL levels. This
5,529 men (aged 45–64 years) without year predicted MACE risk of <7.5 per- legitimizes current guidelines which
pre-existing vascular disease at base- cent at baseline, who would usually be recommend treating this population
line. During the randomized-trial phase, ineligible for statins. with statins,” said study principal in-
participants received either pravastatin vestigator Professor Kaushik Ray of the
40 mg/day or placebo for 4.9 years. “Among placebo-treated patients School of Public Health at Imperial Col-
[Circulation 2017;doi:10.1161/CIRCU- with LDL-C ≥190 mg/dL the observed lege London in London, UK.
LATIONAHA.117.027966] risk of MACE at 5 years was already 7.5
percent, ie, double what would have “Nowadays it would be unethical to
At the end of the randomized-trial been predicted using a risk calculator,” perform a placebo-controlled trial in the
phase, participants with LDL-C levels observed the researchers. However, population with LDL-C ≥190 mg/dL …
≥190 mg/dL who received pravastatin this risk was reduced to 4.8 percent Our findings provide the first trial-based
had a 27 percent reduced risk of CHD in those receiving pravastatin, corre- evidence to support the guidelines for
(p=0.033) and a 25 percent reduced sponding to a 38 percent risk reduction treating patients with LDL above 190
risk in major adverse cardiovascular (p=0.018). mg/dL and no signs of heart disease,”
events (MACE; p=0.037) compared said Ray and co-authors. “Our analysis
with those receiving placebo. “These data reinforce the notion firmly establishes that controlling LDL
that among patients with a LDL-C over time translates to fewer deaths in
Over 20 years of follow-up (15 years ≥190 mg/dL, the observed risk is this population.”
post-trial), the risk of CHD death was much greater than would be predict-
significantly reduced by 28 percent ed through a risk calculator, and thus
(p=0.020), risk of cardiovascular (CV) global risk estimation is not neces-
death by 25 percent (p=0.009), and sary,” they added.
risk of all-cause mortality by 18 per-
cent (p=0.004) among participants with Nonetheless, the researchers ac- *WOSCOPS: West Of Scotland Coronary Prevention
Study
LDL-C ≥190 mg/dL in the pravastatin knowledged that the 15-year post-trial **ACC/AHA: American College of Cardiology/
vs the placebo arms. follow-up was observational and sub- American Heart Association
7
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CONFERENCE COVERAGE
Asian Federation of Osteoporosis Societies (AFOS 2017) 5th Annual Scientific Meeting
October 6-8 • Kuala Lumpur, Malaysia
Genetic advances in osteoporosis:

What’s next?
ELVIRA MANZANO mass, likely due to high bone turnover. variants in AFF cases vs controls. “How-
O
[Nature 2015;526:112-117] ever, analyses were restricted to the
steoporosis is an age-related variants with minor allele frequencies
complex disease with a strong Other genes have been identified less than 3 percent, which limited the
genetic component. However, through studies of rare monogenic disability to make meaningful inferences
the genes responsible for the disease orders affecting the bone, namely CO- about individual variants,” he added.
remain poorly defined, says an expert L1A1/COL1A2 and 13 other genes in
at AFOS 2017. osteogenesis imperfecta; SEC24D and A recent whole exome sequencing
P4HB in Cole-Carpenter syndrome; (WES) study in three sisters who devel-
“The 95 genes/loci identified in the FKBP10, PLOD2 in Bruck syndrome; oped AFF while taking bisphosphonates
largest genome-wide association study CLCN7, TNFSF11, and 5 other genes and three unrelated AFF cases showed
(GWAS) to date can only explain 5.8 per- in osteopetrosis; CTSK in pycnodys- a p.Asp188Tyr mutation in the GGPS1
cent of the genetic contribution to bone ostosis; SOST in sclerosteosis and gene, which is critical to osteoclast
mineral density [BMD] variability,” said van Buchem disease, LRP5 in high function in the mevalonate pathway.
Professor Peter Ebling from the Depart- bones mass syndrome and osteopo-
ment of Medicine at the School of Clin- rosis-pseudoglioma syndrome, and “In two targeted ALPL gene se-
ical Sciences, Monash University, Aus- NOTCH2 in Hadju-Cheney syndrome, quencing studies, an ALPL heterozy-
tralia. As for the majority of the candidate said Ebeling. gous mutation was found in one case,
genes identified from GWAS, additional but not in the other,” Ebeling reported.
biological evidence of their involvement Search for candidate “Targeted sequencing of ALPL, CO-
in bone fragility still lacks, opening up an genes continues L1A1, COL1A2, and SOX9 genes in
opportunity for more research. The search for the genetic basis of five AFF cases has identified a variant in
extreme cases of non-syndromic idio- COL1A2 in one out of five cases.”
pathic osteoporosis has also led to the
identification of several genes – LRP5, Future directions
DKK 1, and WNT3A linked to juvenile Ongoing studies that can leverage
osteoporosis; LRP5, MTHFR to preg- well-phenotyped cases and controls in
nancy and lactation-associated osteo- sufficient numbers are needed to de-
porosis; PLS3 to X-linked osteoporosis; tect rare variants associated with AFFs,
and WNT1 to early-onset autosomal while not overlooking the possibility that
dominant osteoporosis. [Arch Endocri- common variants in multiple genes may
nol Metab 2016;60:391-401] also come into play, said Ebeling.
“As for atypical femoral fractures “We certainly need new drug devel-
Prof Peter Ebeling [AFF], genetic factors may also play an opment to circumvent AFF. To add to
important role in the pathogenesis of that, the Biomarkers Consortium Bone
In one study, EN1, a low frequency the disease,” said Ebeling. “The associ- Quality Project is also attempting to
non-coding genetic variant near a novel ation of AFF with seven rare monogen- qualify a surrogate marker for fracture
locus, was identified and found to have ic bone diseases, including that linked prediction for use in clinical trials, obvi-
an effect size that is fourfold larger than with the COL1A1/COL1A2, CTSK, ating the need for multiple large RCTs
the mean of previously reported com- PLS3 and LRP5 genes, supports this with fracture as an endpoint.”
mon variants for lumbar spine BMD. concept.”
EN1 was also associated with a de- If a surrogate marker is approved
creased fracture risk (odds ratio [OR], A pilot study using an exome array for osteoporosis drug development,
0.85). In an EN1 mouse model, condi- in 13 patients with AFF and 268 controls that will push new therapies into the
tional loss of EN1 resulted in low bone identified a greater number of rare gene market, Ebeling concluded.
8
16
CONFERENCE COVERAGE
Drug holiday for osteoporosis:

Who, when, how long?
ELVIRA MANZANO
B
isphosphonates have proven
antifracture efficacy and remain
to be the cornerstone of oste-
oporosis treatment. However, a drug
holiday is of particular importance with
bisphosphonates due to some signals
with long-term use of the drug, includ-
ing rare incidence of atypical femoral
fracture (AFF) and osteonecrosis of the
jaw (ONJ), says a leading endocrinolo-
gist at AFOS 2017.
This raises questions on the need

for intermittent discontinuation of bis-
phosphonate treatment after long-term
use. The European Medical Association
(EMA), in its position statement pub-
lished this year, specifies that discon- Quality of Life Working Group advises ment may be restarted. Alternative
tinuation of bisphosphonates should be clinicians managing patients with oste- therapy may be used for individuals at
considered in all patients with osteopo- oporosis to individualize treatment de- high risk of fractures. [J Bone Metab
rosis after >5 years of treatment with cisions based on risk factors such as 2015; 22:167-174]
alendronate, risedronate or zoledronic bone density, clinical risk factors, and
acid, said Professor Leilani Merca- history of incident fractures. The group, Drug of choice for
do-Asis from the University of Santo To- however, could not agree on the du- osteoporosis fractures
mas, Manila, Philippines. “If the patient ration of holiday and how to monitor “To put this into proper perspec-
has not had fractures before or during treatment once on a drug holiday. [Os- tive, bisphosphonates, in my opinion,
therapy and the fracture risk is low, a teoporos Int 2016;27:849] remain to be the drug of choice for pre-
drug holiday can be recommended.” vention and treatment of osteoporotic
As responses to antiresorptive ef- fractures,” said Mercado-Asis. “The
However, if a new fracture is experi- fects differ among Asians vs Cauca- primary action of bisphosphonates
enced or a fracture risk has increased, sians, South Korea issued a position is hitting an important physiological
and BMD remains low (femoral neck statement which states that drug holi- mechanism – bone remodeling – which
T-score ≤-2.5), anti-osteoporotic treat- day may be considered after 5 years of is crucial in maintaining bone strength
ment should be resumed, she added. alendronate and risedronate treatment, and durability.”
and after 3 years of zoledronic acid in
The human IgG2 monoclonal anti- individuals who are not at high risk of AFF and ONJ, though rare, are
body denosumab also has a good an- fracture. However, treatment should apparent side effects that are causing
tifracture efficacy. “In cases of denos- be continued in patients at high frac- realistic concerns, she added. “Drug
umab discontinuation, close monitoring ture risk. Annual bone mineral density holiday remains controversial and are
is suggested due to the possibility of (BMD) monitoring is recommended subject to debates. Individualizing treat-
rebound fractures,” said Mercado-Asis. during drug holiday. If there are signif- ment regimen according to the degree
icant reductions in BMD, or if T score of risks is of immense value. Instead of
Meanwhile, the International Os- reaches <2.5, or new osteoporotic stopping bisphosphonates, should we
teoporosis Foundation Epidemiology/ fractures occur, bisphosphonate treat- consider alternative treatment?”
9
17
CONFERENCE COVERAGE
Best practices in assessing BMD

PEARL TOH tioned Carey. “Providing appropriate
A
“For the spine, it should be straight, training, certification, and support to
ccurate and reliable measure- centred, includes anatomical landmarks DXA technologists and interpreters can
ments of bone mineral density [in the spine like] T12 [to the entire L1- help assure quality bone densitometry.”
(BMD) are important to en- L4 region], and like the upper margins
sure validity of results, and clinicians of the sacroiliac joints. There should be On the other hand, the flipside of
should adhere to available standards no movement or artefacts present, sim- having a low-quality BMD testing is
to achieve this, said Dr John Carey, ilarly to other regions.” having an overdiagnosis, he said. “We
president of the International Society get credit for curing diseases that nev-
for Clinical Densitometry (ISCD) during According to the ISCD position er would have harmed the patient. And
AFOS 2017. paper, the preferred skeletal sites for we do see collateral damage of our
taking BMD measurements in children well-intentioned efforts.”
“Quality BMD testing entails testing are the lumbar spine and total body,
the right people, performing accurate less the head. In adults, femoral neck, To avoid pitfalls in densitometry
and reliable test, preparing high-quali- lumbar spine (L1-L4), and total hip are testing, healthcare professionals should
ty report … This will improve diagnosis the preferred sites, while the distal 1/3 strive to become an expert through
and treatment of those most likely to radius is also recommended in some training, reading and case discussion,
benefit, and reduce or avoid unneces- instances, highlighted Carey. apply ISCD quality measures for scan-
sary testing or treatment among those ning patients and interpreting their re-
least likely to benefit,” he said. The ISCD position paper also states sults, keep up-to-date with ISCD cours-
that post-menopausal women and men es, certification, publication, and take a
When scanning the hip, optimal of >50 years can be diagnosed using good patient history, advised Carey.
positioning and necessary attributes the T-score while for younger men and
are important, emphasized Carey. “Put premenopausal women, the Z-score is Concluding his talk with humour,
simply, that means having a straight recommended instead. Carey said, “In life, you only need three
femoral shaft with correct femoral rota- bones – a back bone, a funny bone,
tion, there should be no obvious arte- “If you have had a fragility fracture and a wishbone.”
facts and motion, and the greater tro- [previously], clearly you already have
chanter should be centred and situated osteoporosis. … [In this case,] DXA* *DXA: Dual-enery X-ray absorptiometry
vertically. You should be able to see a is not used for diagnosis, it is used for
little lobe at the left of the trochanter if it monitoring and assessing prognosis.
is rotated appropriately.” For people who haven’t had a fracture,
Podcast with
you can also use DXA to assess risk of
AFOS president
fracture,” said Carey. Dr Fen
Lee Hew
Repeated measures require knowl-
edge and further refinements of the
least significant change (LSC), he ex-
plained, adding that the acceptable Podcast with
orthopaedic
standards for LSC are <6.9 percent
surgeon Dr Joon
for femoral neck, <5.0 percent for total Kiong Lee
proximal femur, and <5.3 percent for
the lumbar spine.
How to avoid pitfalls

“The only thing that is worse than
not having access to BMD test is hav-
Dr John Carey ing access to a really bad one,” cau-
18
10
11
CONFERENCE COVERAGE
Treatment failure in osteoporosis:

What can be done?
ROSHINI CLAIRE ANTHONY PINP but a significant decrease in BMD. tures, current smokers and those with
T
In these situations, the Working Group baseline alkaline phosphatase total ac-
reatment failure in osteoporosis recommended a change of treatment. tivity levels ≥66.5 U/L were at elevated
remains a problem, even among [Osteoporosis Int 2012;23:2769-2774] risk of bisphosphonate treatment fail-
patients who are treatment-ad- ure (OR, 3.22; p=0.034 and OR, 4.22;
herent, according to a presentation at If the patient is not meeting good p=0.007, respectively). [Osteoporosis
AFOS 2017. response criteria within a year of treat- Int 2014;25:1401-1410]
ment initiation, treating physicians
“The fundamental purpose of os- should ensure that the patient is com- Future research goals
teoporosis treatment is to reduce the pliant and rule out occult secondary In order to address treatment fail-
risk of fracture. Available effective treat- osteoporosis, said Yang. Following ure, the causes of treatment failure
ments only reduce fracture incidence this, the IOF Working Group suggests need to be determined, and new frac-
by 20–60 percent, thus fractures do treatment modifications such as re- tures, BMD, and bone turnover mark-
occur during treatment,” said Profes- placing a weaker antiresorptive agent ers should be treated, said Yang, who
sor Yang Rong-Sen from the National with a stronger one from the same advocated for more research into de-
Taiwan University and Hospital, Taipei, class, replacing an oral drug with an termining the factors behind treatment
Taiwan. [AFOS 2017, abstract SA5.1] injectable one, or replacing a strong failure.
antiresorptive agent with an anabolic
While multiple factors contribute to agent. Nonetheless, choice of substi- Among the causes of treatment
fractures, some patients may still expe- tuted medication following treatment failure are poor bone responders, inap-
rience failure with available treatment failure would differ from one drug to propriate treatment, poor compliance,
despite high compliance. Medication another, said Yang. [Osteoporosis Int medication inefficacy, and fall-related
cannot treat everything, he said. 2012;23:2769-2774] injuries, he said.
“Bisphosphonates [for example] Risk factors for treatment “We still need a consensus on treat-
improve some bone biomechanical pa- failure ment failure,” said Yang. “[With the con-
rameters, but not non-skeletal risk fac- Risk factors for treatment failure sensus], we may be able to detect true
tors for fracture such as falls, genotype, vary according to patient, as well as inadequate responders to osteoporosis
comorbidity, … and advanced age,” he by medication type. In a retrospective treatment, identify possible associated
said. study of patients with rheumatoid ar- factors in individual patients, act on
thritis and osteoporosis, nonadherence individual additional factors to improve
According to Yang, the International to bisphosphonates was the main risk outcomes, determine the intervention
Osteoporosis Foundation (IOF) Inade- factor for treatment failure. [Mod Rheu- threshold, and choose the most suit-
quate Responders Working Group de- matol 2016;26:194-199] able medication for a given patient. The
fined treatment failure as, after exclud- goal is treat to target,” he said.
ing secondary osteoporosis or maximal In a retrospective study of individ-
treatment adherence, ≥2 incident fragil- uals with osteopenia or osteoporosis, Integrated approaches are neces-
ity fractures; or one incident fracture ac- prior bisphosphonate or vitamin D use sary, said Yang.
companied by elevations in the serum (odds ratio [OR], 1.50 each; p<0.05)
levels of the biomarkers C-telopeptide were risk factors for teriparatide treat- We could also develop treat-to-
of type I collagen (CTX) or procollagen ment failure, as determined by BMD target and fall prevention strategies for
type I N propeptide (PINP) at baseline change. [Bone Rep 2015;4:17-22] individual patients and assess and act
with no significant reduction during on clinical risk factors. Importantly, we
treatment or a significant decrease in In a study of postmenopausal wom- need to identify the real response and
bone mineral density (BMD) or both; or en with previously untreated primary the effectiveness of initiating a new
no significant decrease in serum CTX or osteoporosis and at high risk for frac- therapy, he said.
12
20
CONFERENCE COVERAGE
1 in 4 men has osteoporosis, yet most

underdiagnosed
PEARL TOH men (mean age 64.58 years, 33.3 per- p=0.012), family history of osteoporo-
A
cent overweight and 11 percent obese) sis (4.6 percent; p=0.044), and histo-
bout one in four men in the Phil- who underwent dual-energy X-ray ab- ry of fracture (21.5 percent; p<0.001)
ippines had osteoporosis but sorptiometry (DXA) scan at the Universi- were significantly associated with an
many were underdiagnosed, ty of Santo Tomas Hospital in the Philip- increased risk of osteoporosis in the
with old age (>70 years), history of frac- pines. [AFOS 2017, abstract PC25] male cohort.
ture, and family history of osteoporosis
being the main risk factors for develop- Based on DXA scanning, 39.7 per- Other risk factors such as inade-
ing the condition, according to a study cent had low bone mass or osteopenia, quate calcium intake (33.9 percent),
presented at AFOS 2017. 26 percent had osteoporosis, and 19.2 smoking (32 percent), and weight
percent had severe osteoporosis. Ac- loss of >10 percent (incidence, 30
“Osteoporosis in men similarly con- cording to the researchers, the overall percent) were not significantly associ-
tribute to significant morbidity and mor- prevalence of osteoporosis of 26 per- ated with increased osteoporosis risk
tality-associated fractures. However, cent was consistent with data from Eu- in the cohort.
these are commonly underdiagnosed rope, Saudi Arabia, and Brazil.
and undertreated with still considerable “This study showed that men less
limited studies,” noted co-authors Drs “Similarly to women, osteoporosis than 60 years old had comparable prev-
Ma. Imee Esquibel and Julie Li-Yu from in men is underdiagnosed due to lack alence to those more than 70 years old
the University of Santo Tomas Hospital of evident symptoms especially among especially those with risk factors. This
and De Los Santos-STI Medical Center the elderly,” observed Esquibel and Li. suggests that clinicians might need to
in Manila, Philippines, respectively. screen males younger than 70 years
Among the risk factors studied, age old especially those with risk factors,”
The retrospective study involved 219 of >70 years (incidence, 64.8 percent; said Esquibel and Li.
21
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CONFERENCE COVERAGE
Trabecular bone score not lower in T2D

ROSHINI CLAIRE ANTHONY
P
atients with type 2 diabetes (T2D)
may not necessarily have low-
er trabecular bone scores (TBS)
than nondiabetics, a finding that con-
trasts with that of previous research,
according to a study published in a
poster at AFOS 2017.
“TBS is an attempt to measure

quantitatively bone microarchitecture,
which can be a measure of bone quality
in the lumbar spine,” said study inves-
tigator Dr Yeap Swan Sim, a consul-
tant rheumatologist from the Puchong
Medical Specialist Centre in Selangor,
Malaysia.
“Previous studies have found being similar in both the fracture and dian T2D duration 10 years) with 56
TBS scores to be significantly lower non-fracture group. So, the use of TBS nondiabetic patients (mean age 60.55
in subjects with diabetes which is in is an additional measurement that may years) who had undergone BMD mea-
contrast to this study,” said Yeap and be able to detect patients with altered surement between December 2008 and
co-authors. [J Clin Endocrinol Metab bone microarchitecture who may be at June 2017. Patients with conditions that
2015;100:475-482] risk of fracture, despite similar BMD,” could potentially affect bone and calci-
said Yeap. um metabolism or those on bone-af-
In this study, TBS was comparable fecting medications were excluded from
between patients with T2D and those Fracture Risk Assessment Tool the study. BMD did not differ between
without (1.289 vs 1.327; p=0.087). The (FRAX) scores also significantly differed diabetic and nondiabetic patients.
researchers noticed a correlation be- between patients with and without T2D
tween age and TBS (p=0.009), as well (median, FRAXmajor with TBS, 7.40 vs “In other studies with T2D patients,
as a lower TBS among patients with a 3.40; p=0.007, FRAXhip with TBS, 2.45 they had lower TBS levels compared
prior history of fracture (median, 1.210 vs 1.00; p=0.032, and FRAXmajor without to non-T2D patients, which could be a
vs 1.327; p=0.001). [AFOS 2017, ab- TBS, 7.10 vs 4.20; p=0.016). marker of altered bone quality in T2D.
stract PC23] This may explain the higher fracture risk
However, there was no significant in T2D patients without much difference
While there was no significant dif- difference between T2D and non-T2D in the BMD measurements. However,
ference in lumbar spine bone mineral patients in terms of FRAXhip without we did not show this difference in this
density (BMD) between patients with TBS (median, 2.00 vs 1.20; p=0.061). study, which we think may be due to …
or without prior fracture, patients with non-T2D patients [being] younger than
a previous fracture had significantly “There were differences in the the T2D patients,” said Yeap.
lower femoral neck and total hip BMD FRAX scores calculated with and with-
(p<0.0001 for each comparison). out TBS but the differences were small As these results were from a sin-
and may not be clinically significant,” gle-centre study, Yeap said there are
“TBS values were lower in pa- said the authors. plans to research this on a wider scale,
tients who had a fracture compared though the current lack of TBS soft-
with those who had not. In our popu- The study compared 56 patients ware at many institutions may impede
lation, this was the case despite BMD with T2D (mean age 67.4 years, me- this plan.
14
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CONFERENCE COVERAGE
Canal-to-diaphysis ratio useful for assessing

hip fracture risk in the elderly
JAIRIA DELA CRUZ
T
he canal-to-diaphysis ratio (CDR)
appears to be a reliable indicator
of hip fracture risk in the elderly,
with a CDR of 0.60 associated with an
increased risk, according to a study.
Besides being reliable, evaluating

the CDR is an inexpensive and acces-
sible means of stratifying the risk of hip
fracture in the elderly. This is particular-
ly relevant in Asia, where most of the
countries are still underdeveloped and
have limited resources, said the team
of investigators from the Hospital Raja
Permaisuri Bainun in Perak, Malaysia.
In the study, the team measured

CDR from hip X-rays of 50 patients
(mean age 76.22 years; 72 percent
female) with trochanteric fractures and ceptable correlation between CDR derly individuals to prevent hip fracture
50 controls (mean age 74.32 years; 56 and age, indicating an increase in CDR and improve the quality of life in this pop-
percent female) without fracture. The with advancing age. ulation, as CDR is a simple method of
contralateral, intact side of the hip was calculation that can be taught and under-
”
used in the patients to avoid errors. stood by all levels of medical personnel.
“ Larger scale studies
Obtained at a point that was 5 Nevertheless, larger scale studies
cm distal to the midlesser trochan-
are needed to further are needed to further establish the rela-
ter on an anteroposterior view, CDR establish the relationship tionship between CDR and hip fracture
measurements revealed a significant between CDR in osteoporotic patients as confirmed
difference between the fracture and and hip fracture in by dual-energy X-ray absorptiometry
control groups (0.13 vs 0.14 SD, re- evaluation, they added.
spectively; p=0.001). [AFOS 2017,
osteoporotic patients”
abstract BPA 01]
At a CDR index of 0.60, the risk of The present study demonstrates a Scan this QR
code for full
a hip fracture was fourfold greater in significant direct relationship between
coverage of
the fracture group than in the control CDR and hip fracture risk, the investi- AFOS 2017.
group. This suggests that individuals gators said. “Patients with CDR >0.60
with CDR >0.60 are at a greater risk of should be given extra attention in treat-
trochanteric fracture, the investigators ing osteoporosis as they are at a higher
said. risk of fracture.”
In addition, a Pearson correlation The investigators are optimistic that

coefficient of 0.843 showed an ac- CDR can facilitate wider screening of el-
15
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CONFERENCE COVERAGE
Balloon kyphoplasty safe, effective for OVF

STEPHEN PADILLA
E
lderly patients with osteoporotic
vertebral fractures (OVF) should
refrain from undergoing highly in-
vasive surgery, but those with no poste-
rior wall mobility or paralysis may ben-
efit from balloon kyphoplasty (BKP) for
OVF with posterior vertebral wall dam-
age, according to a study presented at
AFOS 2017.
There was no mobility of middle col-

umn in either preoperative standing or
dorsal lateral view in any of the patients
included in the study. An improvement
was observed in the lumbar pain visual
analogue scale (VAS), from a preopera-
tive mean score of 8.5 (range, 7–10) to
a postoperative mean of 2 (0–7). [AFOS
2017, abstract BPA 03]
In five patients, neurological symp-

toms were improved. Furthermore, all
patients who had had difficulty in main- nal canal also occurs after BKP. [Injury In all participants, the posterior ver-
taining the sitting posture became am- 2014;45:1539-1544] tebral wall protruded into the vertebral
bulatory following surgery. Activities of canal. The posterior vertebral wall had
daily living (ADL) scores did not vary, In the current study, “as for the ver- a mean spinal cord occupation rate of
with a mean preoperative score of 8.7 tebral canal occupation rate, results 38.2 percent (21–54 percent). The oc-
(0–9) and a mean postoperative score did not have a difference either,” the cupation rate was ≥20 percent but <40
of 8.6 (7–12), which suggested no cor- researchers said. percent in four patients, and ≥40 per-
relation with the spinal cord occupation cent but <60 percent in five patients.
rate of the middle column. A total of nine patients (mean age
at the time of surgery 81 years; 8 Researchers evaluated pre- and
Complications were reported in women) were included. The mean du- postoperative imaging findings,
four patients. Two participants had ration of postoperative follow-up was scores on the lumbar pain VAS, and
bone cement leakage in the lateral 8.6 (1–24) months, and the mean du- ADL score (ADL part of the Japan Or-
vertebral wall, with no symptom ag- ration between onset and surgery was thopedic Association scoring system)
gravation, and the other two had ad- 3.6 (1–7) months. in these patients.
jacent vertebral fracture that required
a brace. Preoperative neurological symp- “The limitation of our study was that
toms presented in five patients (epico- the number of our cases was small,” re-
In an earlier study, Gan and col- nus in two patients, cauda equine in searchers said.
leagues concluded that BKP is a safe one, and nerve root in two). There were
and effective method for OVF with six patients who had difficulty in main- BKP is indicated for the treatment
middle column compromise but with- taining the sitting posture. The fractured of OVF, in which the middle column is
out neurological deficit. In addition, vertebral body was T6 in one patient, often damaged during conservative
spontaneous remodelling of the spi- T12 in two, L1 in five, and L4 in one. therapy, they explained.
24
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CONFERENCE COVERAGE
FLS may improve outcomes in patients

with osteoporotic fracture history
F
racture liaison services (FLS) im-
proved outcomes in older individ-
uals with a history of osteoporo-
sis-related fractures, according to a
systematic review and meta-analysis.
“[FLS] are coordinator-based mod-

els of secondary fracture prevention
services,” said study author Dr Pau-
lo Wu Chih-Hsing from the National
Cheng Kung University College of Med-
icine and Hospital in Tainan, Taiwan,
and colleagues.
“[FLS] are designed to identify pa-

tients who are considered to be at
increased risk of subsequent or sec-
ondary fractures, and, following a com-
prehensive assessment, ensure that
patients initiate appropriate treatment
via improved care coordination and weighted average rate, 23.5 percent said the researchers. Moreover, a ma-
communication,” he said. [non-FLS] vs 48.1 percent [FLS]), treat- jority of the studies were conducted in
ment initiation (unweighted average Western populations, limiting the gen-
”
rate, 17.2 percent vs 38.0 percent), and eralizability of the data, they said, call-
“FLS play a significant treatment adherence (unweighted aver- ing for further research in non-Western
age rate, 34.1 percent vs 57.0 percent). populations as well as studies evaluat-
role in minimizing
ing long-term outcomes of FLS.
the burden of The findings were presented as a
osteoporosis” poster at AFOS 2017. “The results of our systematic litera-
ture review and meta-analysis suggest
Studies included in the analyses that FLS programmes have improved
Compared with non-FLS controls, were limited to 74 randomized and the management of osteoporosis,
individuals who used FLS demonstrat- nonrandomized trials, and retrospective resulting in significant reductions in
ed reductions in the absolute risk of re- and prospective observational studies, refracture and mortality rates and sig-
fracture (unweighted average refracture with studies on primary fracture preven- nificant increases in BMD testing, treat-
rate, 13.4 percent [non-FLS] vs 6.4 per- tion and other bone diseases excluded. ment initiation rates, and adherence,”
cent [FLS]) and absolute risk of mortal- Study participants were age ≥50 years said Wu and co-authors.
ity (unweighted average mortality rate, with previous osteoporosis-related
15.8 percent vs 10.4 percent). [AFOS fractures. “FLS are clinically effective across a
2017, abstract PC 26] range of clinically important outcomes
The observational nature of many in patients with osteoporosis, therefore
Individuals using FLS also demon- included studies as well as variations indicating that FLS play a significant
strated increases in the rates of bone in baseline characteristics among the role in minimizing the burden of osteo-
mineral density (BMD) testing (un- patients may have affected the results, porosis,” they said.
17
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CONFERENCE COVERAGE
13th Asian-Pacific Congress of Hypertension (APCH) • October 6-8 • Singapore
BP target for stroke prevention in Asians

PEARL TOH get for preventing stroke in Asians, ac-
F
cording to Ramani.
or stroke prevention in an Asian
population, a blood pressure (BP) Based on the COPE* study in Ja-
of <140/90 mm Hg is a reason- pan, individuals with a BP of <140/90
able target and particularly, 120-130/80 mm Hg had a reduced risk of stroke
mm Hg may be optimal, according to a than those with a BP of >140/90 mm
presentation at the APCH 2017 Meet- Hg. [J Hypertens 2011;29:1649-1659;
ing in Singapore. Hypertens Res 2013;36:1088-1095]
This finding is supported by the FE-
“BP targets for stroke prevention VER** study involving 9,800 Chinese,
are based largely on trials performed which shows reductions in the risk of
in non-Asian populations,” although both fatal and nonfatal stroke by 27
the highest global stroke mortality rate percent (p=0.001), all cardiovascular
occurs in Asia (particularly in Mongo- events by 35 percent (p=0.012), and
lia, Russia, China, and Southeast Asia) cardiovascular death by 33 percent
and that the risk of stroke was higher in (p=0.019) in subjects who achieved
hypertensive Asians than Caucasians, an average BP of 137.3/82.5 mm Hg
noted Dr Narayanaswamy Ramani from vs 142.5/85 mm Hg. [J Hypertens CSPPT*** study on 17,280 Chinese
Raffles Hospital, Singapore. [Hyperten- 2005;23:2157-2172] suggests a J-curve relationship be-
sion 2007;50:991-997] tween SBP and stroke risk: Compared
with participants who achieved an
”
“Hypertension is a strong risk fac- on-treatment SBP of 120–130 mm Hg,
tor for stroke, more so among Asians “Hypertension is a the risk of first stroke was increased
… In addition, advance age com- strong risk factor with SBP of 130–135 mm Hg (HR,
pounds the risk – older persons with for stroke, more so 1.63), 135–140 mm Hg (HR, 1.85) and
higher BP have [an even] higher risk particularly, <120 mm Hg (HR, 4.37).
of stroke,” said Ramani. As hyperten-
among Asians” [Hypertension 2017;69:697-704]
sion is the most modifiable risk factor
for stroke, BP lowering is important for In general, there are limited random-
stroke prevention. These data suggest that a BP tar- ized clinical trials on Asians, with most
get of <140/90 mm Hg is reasonable, of the trials done in China or Japan,
However, there is no clear answer and probably even a BP of <140/80 observed Ramani. However, Asians
as to what should be the ideal BP tar- mm Hg, for stroke prevention in Asians, consist of many different populations
said Ramani. besides Chinese and Japanese, and
hence, more trials are needed in other
Nonetheless, some studies have Asian populations, he continued.
demonstrated conflicting results, with
the JATOS trial in Japan showing that “The CSPPT trial suggests that a
achieving a systolic BP of <140 mm Hg BP target of 120–130/80 mm Hg may
is no better than 140–160 mm Hg, while be optimal in Asians … but more stud-
the VALISH study in Japan suggests no ies are needed,” he said, suggesting an
difference in stroke risk between those BP target of <130/80 mm Hg for pre-
with <130, 130–145, and >145 mm Hg venting stroke in Asians who have had
SBP. [Hypertens Res 2008;31:2115- a stroke or transient ischaemia.
2127; Hypertension 2017;69:220-227]
*COPE: COmbination therapy of hypertension to
Prevent cardiovascular Events
Notwithstanding the contradictory **FEVER: Felodipine EVEnt Reduction
Dr Narayanaswamy Ramani findings from JATOS and VALISH, the ***CSPPT: China Stroke Primary Prevention Trial
18
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CONFERENCE COVERAGE
Reducing salt intake in Asia-Pacific essential

for blood pressure control
AUDREY ABELLA Salt intake cannot be avoided as we
R
are passive salt consumers, noted Mac-
educing salt intake, particu- Gregor. Given this, as well as the strong
larly among individuals in the correlation between salt intake and hy-
Asia-Pacific (APAC) region, is of pertension, government/public health
paramount importance as it is essential education and media campaigns are
for alleviating hypertension, according strongly advocated to reduce popula-
to a presentation at APCH 2017. tion BP and control high BP through salt
intake reduction. “If we did [these] strat-
“There is an urgent programme to egies, [even small BP reductions can
reduce salt intake … [in APAC which] lead to] a massive reduction in strokes,
has the highest salt intake in the world, heart failure, and heart attacks.”
particularly in northern China, northern
Japan, and Korea where salt intake is In a school-based randomized study
extremely high,” said Professor Gra- in China, salt intake decreased by an
ham MacGregor from the Wolfson Insti- average of 2 g/day (from 7 to 5 g/day) in
tute of Preventive Medicine in the UK. children who were educated about the
“In the UK, [we believe that] salt added dangers of salt, and by 3 g/day (from pact the public and guide them towards
to food is a chronic poison that slowly 12 to 9 g/day) in adult family members a healthier lifestyle, noted MacGregor.
[increases] our blood pressure (BP) and whom the children shared their lessons
is a major cause of death and disability with. [BMJ 2015;350:h770] “If this pol- Furthermore, the food industry
particularly through strokes.” icy was long-term and spread across is encouraged to participate in pub-
the whole of China, it would prevent lic health policies that require them to
According to the Global Burden [approximately] 200,000 cardiovascular gradually remove or decrease the ex-
of Disease, hypertension is the sin- deaths per year,” said MacGregor. cessive amount of salt incorporated in
gle biggest cause of death in the their products, noted MacGregor.
world, accounting for about 10 million Additionally, evidence shows that a
deaths per year worldwide. [Lancet 5–6 g reduction in salt intake may pre- Salt intake regulation in APAC is es-
2012;380:2224; JAMA 2017;317:165]. vent approximately 1.5 million stroke sential, said MacGregor, as ‘very little is
There is also evidence showing that the and heart deaths per year in the APAC going on’ as opposed to regions such
risk of stroke or cardiovascular deaths region. [BMJ 2013;346:f1325; Hyper- as the US, Canada, Australia, and Eu-
may start even with a systolic BP of 115 tension 2003;42:1093-1099] rope, which have followed the UK mod-
mm Hg. [Lancet 1990;335:765-774] el, with South America not far behind.
In the UK, an ‘incremental reformu- He expressed interest in collaborating
lation’ programme launched in early with health organizations in APAC to
2000 involved a progressive salt re- share public health programmes being
duction target to 6 g across the whole implemented in the UK.
food spectrum, shared MacGregor.
This project was a success, effectively “We would [like to] give them ad-
managing hypertension and its conse- vice and work with them … to try and
quences, and worked counterintuitively encourage more active salt reduction
as it did not require diet modification, in this area … Every country in the
he added. world must set up a salt reduction pro-
gramme [and] implementing that plan is
The study results and the UK pro- the important thing. It’s the single most
gramme demonstrate how intervention- cost-effective public health measure,”
Prof Graham MacGregor al and educational measures may im- concluded MacGregor.
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CONFERENCE COVERAGE
Timing of medication impacts BP control

TRISTAN MANALAC
A
dministration of a long-acting
medication at the time that is
most suitable for maximum pa-
tient compliance is the best approach
for controlling blood pressure (BP), said
Dr Trefor Morgan at APCH 2017.
If BP control for 24 hours is not cer-

tain, then night-time medication may
have an advantage over daytime med-
ication, he added. What is important is
that it should be “ensure[d], either by
measuring it or by knowing what the
drugs do, that sleep and awake BP is
controlled.”
Citing various reports from the lit- Indeed, many studies group partic- in the body is highly dependent on its
erature, Morgan established a strong ipants into two: the dippers who show dose, and it is highly unusual that drugs
correlative link between the declining the normal decline in BP during sleep work for 24 hours.
BP during sleep and various cardio- and the nondippers who do not show
vascular outcomes such as ischaemic this night-time fall in BP. It is routine practice to administer
stroke, with lower sleep BP predicting medication in the morning and measure
”
better outcomes. its effects a couple of hours after. In this
setup, the peak and adequate BP re-
“To improve BP control,
BP while waking up, on the other sponse is achieved during the day and
hand, is a weak predictor of cardiovas- medications are titrated is typically already gone by the critical
cular events. using the morning BP periods: during sleep and as the pa-
predose measurements tients wake up.
These daily fluctuations in BP may
and administered at night”
be principally explained through the So to improve BP control, medi-
changes in the activity of different con- cations are titrated using the morning
trol systems, Morgan explained. At BP predose measurements and admin-
night, during sleep, the sympathetic Notably, nondippers have been istered at night. That way, “you avoid
nervous system relaxes, resulting in the shown across many studies to have measurement at the highest peak ef-
decline in BP which, in turn, causes the poorer prognosis than dippers, and fect,” Morgan concluded.
renin-angiotensin system to kick in. thus benefit the most from pharmaceu-
tical interventions.
It is important to note that these
trends do not mean that the renin-an- However, “if we have these two im- Scan this QR
code for full
giotensin system is normally turned off, portant systems controlling blood pres-
coverage of
he said. Renin levels also fluctuate with sure with different activities, if we’re us- APCH 2017.
activity and posture during the day. ing drugs that interfere with the activity
of this system, we need to make certain
Moreover, because these changes the drug is present at the time when the
in the activity of the control systems are system is active,” said Morgan.
not universal, they also account for the
interindividual differences in the daily This makes the timing of medication
BP fluctuations. critical because the duration of the drug
28
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CONFERENCE COVERAGE
Accurate diagnosis, treatment important

in resistant hypertension
T
“True resistant hypertension is un- “[The ESC guidelines] emphasized
he prevalence of resistant hy- common after exclusion of pseudo-re- very strongly that all of this is based on
pertension may be lower than sistance and secondary causes,” said observational data or personal opinion,
expected, particularly once Williams, suggesting that the preva- but the evidence base is very low,” he
pseudo-resistant hypertension due to lence may be less than 10 percent of all said.
treatment nonadherence is taken into treated hypertensive patients.
account, according to a presentation at “Resistant hypertension is predom-
APCH 2017. inantly a sodium-retaining state that
”
responds best to additional diuretic
“A key aspect of resistant hyper- “In terms of lifestyle therapy. In patients with an eGFR >60
tension is an accurate diagnosis,” said mL/min, spironolactone 25–50 mg daily
Professor Bryan Williams from Univer-
management, is very effective and generally safe and
sity College London and chairperson high dietary sodium well tolerated, although gynaecomastia
of the European Society of Cardiology consumption can can become a problem in men [with
(ESC) Council on Hypertension. This contribute to resistance longer term use]. Higher dose amiloride
would involve excluding secondary and 10–20 mg daily may be an alternative
pseudo-resistant hypertension, he said.
to hypertension drugs” to spironolactone but the same cave-
[APCH 2017, symposium G] ats apply regarding renal function and
potassium,” said Williams, who under-
Patients with pseudo-resistant hy- scored the need for further research
pertension include those who may not Treating resistant into determining the potential role of
have accurate blood pressure (BP) hypertension other diuretics in managing resistant
measurement (eg, wrong cuff size), Lifestyle modification, BP-lowering hypertension.
those with white coat hypertension, medication, and devices may help in
those receiving suboptimal treatment the management of resistant hyperten- He also pointed out the importance
for hypertension, or those who are non- sion, said Williams. of baseline eGFR and potassium lev-
adherent to treatment. els due to the increased risk of hy-
In terms of lifestyle management, perkalaemia in individuals with eGFR
Common causes of secondary hy- high dietary sodium consumption can <60 mL/min or potassium levels >4.5
pertension are kidney or renal artery contribute to resistance to hyperten- mmol/L, and especially in those with
disease, and aldosterone-producing ad- sion drugs, he said. eGFR <45 mL/min or with potassium
enomas, while less common causes in- levels >5.0 mmol/L. Aldosterone-pro-
clude Cushing’s syndrome, phaeochro- Medication-wise, guidelines pub- ducing adenomas are also a possibility
mocytoma, and monogenic disorders. lished by the ESC in 2013 stressed in patients who respond very well to
the use of diuretics in the management spironolactone.
To identify patients with resistant of resistant hypertension, particularly
hypertension, it must first be deter- low-dose spironolactone. However, the With regards to devices, continuous
mined if the patient is hypertensive and guidelines also highlighted the poten- positive airway pressure or CPAP can
if yes, if the patient is receiving optimal tial for hyperkalaemia with spironolac- be an effective BP-reducing measure if
treatment and adhering to it. Based on tone, especially among patients with a the primary cause of the resistant hy-
the association between a higher num- low estimated glomerular filtration rate pertension is obstructive sleep apnoea,
ber of medications and nonadherence, (eGFR), and suggested eplerenone, said Williams. Evidence also points to
simplifying the treatment (eg, from mul- amiloride, and loop or higher-dose thi- the potential effectiveness of barore-
tiple pills to one) may help. If none of azide-type diuretics as alternatives, as ceptor stimulation, though this measure
these are effective, secondary hyper- well as α- or β-blockers, or centrally is expensive, requires surgical implan-
tension would need to be ruled out, acting agents, said Williams. [Eur Heart tation, and is not well tolerated in some
said Williams. J 2013;34:2159-2219] patients, he said.
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CONFERENCE COVERAGE
Changing BP targets: Evidence vs opinion

PEARL TOH differ greatly, observed Rahman. For in-
C
stance, the ACCOMPLISH trial was not
linical practice is an art guid- mentioned in the NICE guideline, while
ed by good science, and clin- major trials like ASCOT and HOPE were
ical practice guideline (CPG) is not quoted in the ASH/ISH and JNC8
meant to guide in integrating the art guidelines.
and science of clinical practice for the
long-term benefits of patients, said Pro- Not only does the choice of evi-
fessor Abdul Rashid Abdul Rahman, a dence differ, the interpretation of the
consultant cardiovascular physician at evidence may also differ among the
An-Nur Specialist Hospital in Bangi, panellists, which may contribute to the
Malaysia. lack of agreements between guide-
lines, according to Rahman. HYVET, a
“CPG is a document authored col- major trial considered to bear important Prof Abdul Rashid Abdul Rahman
lectively by individuals who individually evidence for elderly patients with hy-
disagreed with what was written,” Rah- pertension was referenced in both the Bridging the gaps
man amused the crowd with a humour ESC/ESH and ASH/ISH guidelines (al- “Gaps existing within the cur-
quote. though it was left out in the NICE guide- rent CPG should be addressed by
line). However, a BP target of <150/90 well-thought out research,” said Rah-
”
mm Hg was recommended for patients man. “We need consensus on how to
aged >60 years in the ESC/ESH guide- choose evidence which matters, how
“We need consensus line but the target age group was >80 to interpret evidence, be guided by re-
on how to choose years in the ASH/ISH guideline. sults from clinically important surrogate
evidence which endpoints in the absence of RCTs, and
matters” “How stringent are we with using conduct definitive RCTs to address
the evidence?” asked Rahman. “Do we specific gaps.”
include only hypertension-dedicated tri-
als or RCTs with adequately powered According to the NICE 2011 re-
Although a general blood pressure clinical outcomes? Do we include only port, research questions that remain to
(BP) target of <140/90 mm Hg is rec- primary outcome trials or meta analy- be answered include out-of-office BP
ommended for all patients with hyper- ses of RCTs?” monitoring, method of assessing life-
tension by major international bodies time cardiovascular risk in those aged
including AHA*, ESC/ESH**, JNC8***, “When it comes to treatment rec- <40 years, and the optimal systolic BP
ASH/ISH#, and NICE##, there have been ommendation, we should only stick to target.
some discords on the ideal BP targets hypothesis-testing studies (not sub-
for specific groups of hypertensive pa- analysis or post hoc analysis).” “Psychosocial and behavioural as-
tients such as those with coronary ar- pects of care must not be neglected,”
tery disease, diabetes, who are elderly, Besides, RCTs-based guidelines reminded Rahman, noting that recom-
or who have previous cerebrovascular do pose some limitations in terms of mendations on lifestyle interventions
accident, he noted. the generalizability to the real-world can be anticipated in the upcoming
scenario, he added, alluding to the NICE guideline due in 2018.
One of the reasons for the discor- frequent exclusion of complicated pa-
dance in existing recommendations tients in RCTs, compliance rates which
lies in the choice of evidence, ie, ran- were often too good, and events rates *AHA: American Heart Association
**ESC/ESH: European Society of Cardiology/
domized controlled trials (RCTs) on which were too low compared with European Society of Hypertension
which the recommendations are based those observed in daily practice. Also, ***JNC8: The Eighth Joint National Committee
on. Among the different committees, generalizability to older or higher-risk ASH/ISH: American Society of Hypertension/
#
International Society of Hypertension

the number and types of major RCTs patients was questionable while Asian ##
NICE: The National Institute for Health and Care
chosen for setting recommendations patients were rarely studied in RCTs. Excellence
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CONFERENCE COVERAGE
Home BP monitoring effective for managing

hypertension
AUDREY ABELLA
H
ome blood pressure (BP) mon-
itoring is important in the man-
agement of hypertension,
especially morning and nocturnal hy-
pertension, according to a presentation
at APCH 2017.
It is extremely important to control

morning BP as it is the strongest in-
dependent predictor of stroke, said Dr
Kazuomi Kario from the Jichi Medical
University Department of Medicine in
Tochigi, Japan. “For stroke and coro- Kario and his colleagues indicated An ICT###-based home BP monitor-
nary artery disease (CAD), morning is that controlling morning hypertension ing system is a potential alternative to
the [riskiest] time [as] BP spontaneously (≥135/85 mm Hg) could be clinically an ambulatory BP monitoring system as
increases in the morning.” relevant in the therapeutic management this will enable patients to self-monitor
of hypertension and in the prevention of their BP levels as shown in the NOC-
Previous evidence has shown a cardiovascular complications. [J Hyper- TURNE* trial. [Circ J 2017;81:948-957;
higher prevalence of silent cerebral in- tens 2017;35:1554-1563; Am J Hyper- Prog Cardiovasc Dis 2016;59:262-281]
farcts and a higher incidence of stroke tens 2005;18:149-151]
events among hypertensive elderly pa- Kario recommended an ICT-based
tients with morning BP surges. [Circu- “Uncontrolled morning BP during stratified strategy to achieve a ‘zero’
lation 2003;107:1401-1406] Moreover, trough effect hours could be a hallmark cardiovascular event rate in the future
Asians were found to have a higher risk of inadequate antihypertensive regimen or a ‘perfect 24-hour BP control’ by
of stroke and CAD compared with Cau- such as the use of short-acting or inter- monitoring the nocturnal BP dipping,
casians, [Hypertension 2007;50:991- mediate-acting drugs, under-dosing of BP variability, and the morning surge.
997] and Japanese individuals par- drugs, or no or low use of combination [Hypertens 2017;31:231-243; Hyper-
ticularly exhibited higher morning BP therapy,” said Kario. tension 2015;65:1163-1169]
levels and BP surges vs Caucasians.
[Hypertension 2015;66:750-756; Circ J On the other hand, uncontrolled “The [individualized] home BP-guid-
2017;81:1337-1345] nocturnal hypertension (sleep sys- ed approach [could] be the best ap-
tolic BP of ≥120 mm Hg), which was proach to increase the quality of man-
found to be associated with a higher agement of hypertension … [I]ts use in
UACR# and NTproBNP##, [Hyperten- clinical care would add considerably to
sion 2012;60:912-928; Hypertension improving hypertension outcomes in
2015;17:340-348] could be the unre- Asia,” concluded Kario.
vealed target of antihypertensive treat-
ment, said Kario.
#
UACR: Urine albumin-to-creatinine ratio
##
NTproBNP: N-terminal pro b-type natriuretic
Given the cardiovascular outcomes peptide
associated with morning and nocturnal ###
ICT: Information and communication technology
hypertension, having access to a home *NOCTURNE: Comparative effects of an angiotensin
II receptor blocker(ARB)/diuretic vs ARB/calcium-
BP monitoring system would help pa- channel blocker combination on uncontrolled
tients achieve the ideal morning and nocturnal hypertension evaluated by ICT-based
Dr Kazuomi Kario nocturnal BP levels, said Kario. nocturnal home BP monitoring
23
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CONFERENCE COVERAGE
Asia Pacific Digestive Week (APDW 2017) • September 23-26 • Hong Kong
Faecal microbiota transplantation effective

for treating inflammatory bowel disease
DR JOSEPH DELANO FULE ROBLES
A
recent study from China showed
that faecal microbiota transplan-
tation (FMT) is effective as a
therapeutic option for patients with in-
flammatory bowel disease (IBD).
“In a self-control study, we demon-

strated positive results 4–6 months
after FMT treatment of patients with
ulcerative colitis [UC]. The clinical re-
sponse rate was 88.2 percent, clini-
cal remission rate was 64.7 percent,
and endoscopic remission rate was
76.5 percent,” reported primary in- Possible mechanisms of FMT in- Significant changes in fungal com-
vestigator Professor Yunshen Yang of clude re-establishment of microbiota position are also observed in IBD.
the People’s Liberation Army General diversity, with increase in Roseburia For instance, a study revealed that
Hospital in Beijing, China, who spoke spp, Oscillibacter spp, Lachtnospira- Basidiomycota spp was significant-
at APDW 2017. [Yang Y, et al, unpub- ceae spp and Ruminococcaceae spp. ly increased whereas Ascomycota
lished data] [Transplant Proc 2016;48:402e407] spp was significantly reduced. [Gut
2017;66:1039-1048]
Significant decreases in Mayo Viruses also play a role in the mech-
scores and endoscopic Mayo scores anism by being detectable as viral Significant expansion of bacte-
were also found as early as 2–3 months contigs transferred from the donors, riophages of the viruses of the Cau-
after FMT (p<0.0001). with none of these viruses replicating dovirales order were noted in IBD
on human cells but scoring as bacte- patients vs healthy controls. [Cell
“A substantial proportion of pa- riophages with Siphoviridae temperate 2015;160:447-460]
tients [76.5 percent] who received phages transferring more efficiently as
FMT also experienced an average compared with other groups. [mBio Recently, probiotics containing
weight increase of 4 kg. Erythrocyte 2016;7:e00322] Escherichia coli Nissle 1917 (EcN) was
sedimentation rate [ESR], C-reactive recommended by guidelines of the Eu-
protein [CRP], white blood cell [WBC] Studies have previously shown that ropean Crohn’s and Colitis Organisation
count, and inflammatory bowel dis- chronic intestinal inflammation develops (ECCO) as an effective treatment alter-
ease questionnaire [IBDQ] also im- in germ-free mouse models after colo- native to mesalazine in maintenance
proved among FMT-treated patients,” nization with commensal gut bacteria. remission among UC patients. [World J
said Yang. IBD patients were found to have fewer Gastroenterol 2016;22:5505-5511]
anti-inflammatory bacteria and more
A recent meta-analysis of 14 co- proinflammatory bacteria in the gut as “Currently, international and local
hort studies and four randomized con- compared with controls. Metabolites of recommendations on FMT are weak
trolled trials also showed higher clinical intestinal microbiota are also disturbed and use of the treatment is limited to
response rate (49 percent vs 28 per- in IBD. Metagenomic studies have sug- clinical research … A lot still need to be
cent; p= 0.02) and clinical remission gested compositional changes of the addressed, such as the mechanism of
rate (28 percent vs 9 percent; p< gut microbiota in patients with IBD. FMT, its safety, indications, preparation
0.01) in IBD patients treated with FMT [World J Gastroenterol 2014;20:14805- of donors, follow-up of patients and
vs placebo. [Aliment Pharmacol Ther 14820; Microorganisms 2016;4:20; Ital ethical implications associated with the
2017;46:213-224] J Pediatr 2014;40:32] procedure,” Yang commented.
24
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CONFERENCE COVERAGE
New endoscopic technologies improve

outcomes of UGIB
NAOMI RODRIG
N
ew endoscopic technologies
have improved outcomes for
patients with upper gastroin-
testinal bleeding (UGIB), according to
Professor James Lau from the Chinese
University of Hong Kong, who reviewed
current treatment practices and latest
advances at APDW 2017.
“Injection therapy with diluted epi-

nephrine, introduced in the 1980s, has
been shown to reduce the need for sur-
gery and transfusion and shorten hos-
pital stay,” said Lau. “Some years later,
we realized that it could be improved by
adding a second modality, such as clips
or thermocoagulation. A meta-anal-
ysis published in 2004 showed that a
second modality not only reduced re-
current bleeding and surgery, but also spray is effective in acute nonvarice- gastric ulcers with limited success, due
decreased mortality by 50 percent. al gastrointestinal bleeding (ANVGIB). to the technical expertise required and
Hence, the current standard is to add “There are no published randomized high rebleeding rates.
a second modality targeting the vessel trials, but a summary of the literature
itself.” [Br Med J 1988;296:1631-1633; indicates that the initial bleeding con- Advances in identifying the stigmata
Gastroenterology 2004;126:441-450] trol rate approaches 90 percent. Un- of recent haemorrhage (SRH) have also
fortunately, the rebleeding rate is 20 improved treatment outcomes. “While
When selecting between clips or percent. The current recommendation in the past we relied on visual interpreta-
thermocoagulation, a meta-analy- therefore suggests haemostatic pow- tion with Forrest classification, new de-
sis showed no significant difference der to stop the bleeding, allowing time vices such as a disposable ultrasound
in terms of bleeding control. [Gut for second-look endoscopy and treat- probe or Doppler probe can better iden-
2007;56:1364-1373] ment of residual stigmata,” noted Lau. tify arterial flow and additional signals.
For example, Doppler probe can identify
“An improved clip that opens to Over-the-scope clips (OTSCs) have nearly 70 percent of clots and 40 per-
about 2 cm provides very nice results. been shown to improve initial bleeding cent of flat spots,” explained Lau. “A re-
You target at the base of the bleeding control vs standard endoscopic thera- cent study suggests that Doppler-guid-
point and push in firmly to apply the py (96 percent vs 62 percent) and re- ed endoscopic treatment is superior to
clip. Two or three clips are usually reduce 7-day rebleeding (24 percent vs standard therapy, but this needs to be
quired,” said Lau. “Coaptive thermo- 33 percent.) “There is an indication that validated in a larger series.” [Gastroen-
coagulation, which involves irrigation, OTSCs are useful in rebleeders, but we terology 2017;152:1310-1318]
pressure on the artery, and thermal are waiting for the full study report,” he
energy, is a technique that withstood remarked. “Reporting of endoscopic ultra-
the test of time as it is still being used.” sound-guided angiotherapy remains
[Gastroenterology 1987;92:1101-1108] The Apollo Overstich – a device for anecdotal, but it is an interesting con-
internal gastric plication used in obesity cept that may be useful in selected pa-
The use of haemostatic powder surgery – has been applied for bleeding tients,” he suggested.
25
33
CONFERENCE COVERAGE
Sodium phosphate tablets preferred over

PEG solution for bowel cleansing
ELAINE TAN
S
odium phosphate (NaP) tab-
lets for bowel preparation prior
to colonoscopy are safe, bet-
ter tolerated by patients, and provide
equivalent and possibly superior co-
lon cleansing compared with standard
polyethylene glycol (PEG) solution, a
Korean study has found.
In the investigator-blinded, con-

trolled study, 62 healthy Korean adults
undergoing elective colonoscopy were
randomized to receive NaP regimen (32
NaP tablets in divided doses) or stan-
dard PEG solution (4 L) for bowel prepa-
ration. Results showed no significant The PEG regimen has been re- who used PEG (50 percent vs 25 per-
difference in total Ottawa Bowel Prepa- garded as the gold standard for bow- cent [p=0.042] and 43.3 vs 12.5 per-
ration Quality Scale (OBPQS) score be- el cleansing, but the need to ingest a cent [p=0.007], respectively).
tween the NaP and PEG groups (4.3 large volume as well as the unpleasant
vs 5.4; p=0.071). Fluid scores (fluid smell and taste of PEG frequently lead Significant fluctuations in serum
quantity in the entire colon), however, to poor patient compliance, resulting in chemistry and electrolytes were noted
were significantly better with NaP vs inadequate bowel preparation. in both groups after bowel cleansing.
PEG upon detailed analysis of individual Patients’ potassium and total calci-
OBPQS scores (0.1 vs 0.6; p<0.001). A “Adequate bowel preparation is es- um levels were significantly decreased
significantly higher proportion of patients sential for swift and complete examina- from baseline in the NaP vs PEG group
in the NaP group achieved adequate tion of the entire colorectal mucosa with (-0.66 mEq/L and -0.45 mg/dL, respec-
bowel preparation, defined as a total minimal complication to avoid missing tively [both p<0.001] vs -0.21 mEq/L
OBPQS score of ≤4 (62.5 percent vs pathologic lesions during colonosco- [p=0.004] and -0.01 mg/dL [p=0.963]),
33.3 percent; p=0.022). [Yonsei Med J py,” said Lee. while inorganic phosphorus levels were
2014;55:1542-1555] significantly elevated in the NaP group
“Low-volume fluid and efficacious (+1.58 mg/dL [p<0.001] vs +0.13 mg/
“Higher satisfaction with the given NaP regimens are popular alternative dL [p=0.18]).
bowel cleansing regimen was reported methods for bowel preparation. How-
by patients in the NaP vs PEG group ever, potential associated risks include “However, the mean changes from
[8.5 vs 5.5 out of 10 on a visual ana- electrolyte imbalances, irreversible renal baseline were generally mild and tran-
logue scale; p<0.001], and significantly dysfunction, and acute phosphate ne- sient, and none of the changes result-
more patients who used NaP indicated phropathy,” Lee explained. ed in serious complications or adverse
willingness to repeat the same regimen events. On follow-up laboratory tests,
in the future [93.8 percent vs 30.0 per- The most common adverse events these changes were found to have nor-
cent; p<0.001]. A less burdensome experienced by patients in the study malized,” noted Lee.
bowel preparation regimen could lead to were nausea, vomiting, abdominal
increased population participation in col- pain, and bloating/distension. No sig- “As our sample size was small and
orectal screening programmes,” report- nificant differences were observed included only outpatients without seri-
ed lead author Dr Seung-Hwa Lee of between the two groups for abdomi- ous comorbidities, further multicentre,
the Ajou University School of Medicine, nal pain and bloating, but nausea and large-scale studies are needed to con-
Suwon, Korea, at AFOS 2017. vomiting were more frequent in patients firm these findings,” said Lee.
26
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CONFERENCE COVERAGE
Immunotherapy: The future in pancreatic

cancer treatment?
JENNY NG therapeutic vaccines, and adoptive T
R
cell therapies such as chimeric antigen
esearchers are setting their receptor T cell therapy,” he continued.
sights high on immunotherapy More recently, the PD-1 inhibi-
as a promising strategy in ad- tor nivolumab, used in combination
vanced pancreatic cancer, with several with nab-paclitaxel and gemcitabine,
agents currently in development. demonstrated encouraging clinical ac-
tivity with low toxicity in patients with
“There is excitement in the use of metastatic pancreatic cancer in a phase
immunotherapy for cancer treatment I study. [J Clin Oncol 2017;35(suppl
because of their mechanism in targeting 4S): abstract 412]
the tumour microenvironment,” said Dr
Thomas Yau of The University of Hong However, Yau warns that immuno-
Kong, who spoke at APDW 2017. therapies are not without side effects.
“PD-1 inhibitors, for example, are as-
For patients with advanced pan- sociated with rash that sometimes re-
creatic cancer, few treatment options quires systemic steroid treatment,” he
are available and chemotherapy-based noted. “Other adverse effects of immu-
regimens remain the standard of care. notherapies include diarrhoea, colitis,
Newer strategies such as nab-pacli- and pneumonitis.”
taxel, a combination of paclitaxel and
albumin used in combination with Within the typical microenvironment, an Until further data on immunother-
gemcitabine to enhance drug delivery immune response would elicit activated apies become available, Yau recom-
to the tumour microenvironment, have T cells to remove the cancerous cells. mends treating advanced pancreatic
demonstrated some survival benefit vs However, pancreatic tumours are able cancer with a gemcitabine-based reg-
gemcitabine alone in both the first- and to activate various immune-suppres- imen (gemcitabine alone or in combina-
second-line settings. However, the me- sive pathways to evade this immune re- tion with nab-paclitaxel or erlotinib) or
dian overall survival for these patients sponse. Immunotherapies act on these FOLFIRINOX (5-FU, leucovorin, irino-
remains less than 1 year. [J Natl Cancer various mechanisms to restore T cell tecan, and oxaliplatin) in the first-line
Inst 2015, doi: 10.1093/jnci/dju413] activity against the tumour. setting, followed by FOLFIRINOX or a
gemcitabine-based regimen, respec-
Research into targeted therapeutic “Pancreatic tumours can evade the tively, upon disease progression.
approaches over the last 10 years have immune system by causing ineffective
yielded only marginal benefits. “Erlotinib presentation of the tumour antigens
is the first and only targeted therapy ap- to the immune system. They can also
proved for treatment of advanced pan- recruit immunosuppressive cells, re-
creatic cancer,” said Yau. “However, its lease immunosuppressive factors or
use is associated with increased toxicity cause T cell checkpoint dysregulation,” Scan this QR
code for full
and most oncologists don’t regard erlo- explained Yau. “The most important
coverage of
tinib as a clinically meaningful treatment components of this tumour microenvi- APDW 2017.
option in advanced pancreatic cancer.” ronment are the myeloid-derived sup-
pressor cells and T regulatory cells.”
Targeting the immunosuppressive
microenvironment of the pancreatic “Immunotherapies currently in de-
tumour may be the key to overcom- velopment for pancreatic cancer in-
ing the high resistance to treatment in clude checkpoint inhibitors, immune
pancreatic tumours, suggested Yau. modulators, monoclonal antibodies,
27
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CONFERENCE COVERAGE
Small bowel bleeding remains

a diagnostic challenge
NAOMI RODRIG
W
hile bleeding from the small
intestine is relatively un-
common, it often presents
a diagnostic challenge. Speaking at
APDW 2017 in Hong Kong, Dr Si-
mon Lo from the Cedars Sinai Medical
Center in Los Angeles, California, US,
reviewed current guidelines and prac-
tices with a special focus on common
pitfalls.
“Small bowel bleeding should be

considered in patients with gastroin-
testinal [GI] bleeding with normal up-
per and lower endoscopic examina-
tions. With evolving technologies in
small bowel imaging with video cap- be performed. [Am J Gastroenterol must also be assessed with deep en-
sule endoscopy [VCE], deep enteros- 2015;110:1265-1287] teroscopy.
copy, double-balloon enteroscopy
[DBE], and radiography, we now have “Intraoperative enteroscopy is the “In patients with Crohn’s disease,
many diagnostic tools available, and most reliable method to examine the strictures might preclude capsule stud-
the guidelines have evolved accord- entire small bowel, with a diagnostic ies and caution is recommended with
ingly,” said Lo. “Unfortunately, some sensitivity of around 80 percent. How- enteroscopic evaluation and treat-
of these technologies are available in ever, the therapeutic efficacy in pre- ment,” suggested Lo.
tertiary-care centres only due to the venting recurrent bleeding is only 41
associated cost, personnel training, percent,” said Lo. “It is also associated Another dilemma is dealing with pa-
and long procedure time.” with significant complications, and pro- tients on anticoagulants who present
longed recovery and hospitalization in with obscure GI bleeding. “When you
The American College of Gastro- about 30 percent of patients.” see bleeding on heparin challenge, you
enterology (ACG) recommends sec- better place a tattoo mark to identify
ond-look examinations using upper “Negative imaging doesn’t mean a the spot,” he advised. “Radionuclide
endoscopy, push enteroscopy, and/ normal small bowel. You never know bleeding scans can pick up very low-
or colonoscopy before small bowel what you would find, as the source grade bleeding, but wrong localization
evaluation. VCE should be considered of the bleeding may not be what it has been reported in up to 25 percent
a first-line procedure for small bowel appears to be. Even trivial-appearing of cases. Furthermore, they are time
examination after other GI sources polyps can still bleed,” he stressed. consuming, and we can’t really use
have been excluded by second-look “In some cases, the diagnosis is not in them to direct treatment.”
endoscopy. Any method of deep en- question, but we still have a problem
teroscopy can be used when there managing the bleeding as it may be “Many challenges remain with eval-
is a strong suspicion of small bowel deep within the lesion.” uations of obscure bleeding, such as
lesion. Intraoperative enteroscopy is cases of prior surgery or altered anat-
a highly sensitive but invasive diag- Patients with Peutz-Jeghers syn- omy, false positive or negative results
nostic and effective therapeutic pro- drome who had undergone multiple with VCE, patients on anticoagulation
cedure; its use should be limited to operations pose a technical challenge. and the risks of intraoperative enteros-
scenarios where enteroscopy cannot Surgical bypasses such as Roux-en-Y copy,” he concluded.
28
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CONFERENCE COVERAGE
53rd European Association for the Study of Diabetes (EASD) Annual Meeting 2017
September 9-15 • Lisbon, Portugal
New test facilitates diagnosis of idiosyncratic

drug-induced liver injury
CHRISTINA LAU
A
new technology involving the
use of monocyte-derived he-
patocyte-like (MH) cells has
demonstrated high sensitivity and
specificity in the diagnosis of idiosyn-
cratic drug-induced liver injury (DILI),
data presented at APDW 2017 have
shown.
“The new MetaHeps test intro-

duced at our department is currently
being evaluated in an ongoing study
with the Chinese University of Hong
Kong,” said Professor Alexander Ger-
bes of the Liver Centre Munich, Mu-
nich, Germany.
MetaHeps involves the use of pe-

ripheral monocytes derived from blood
samples of patients with acute liver in- In the 23 non-DILI patients, MH cell be caused by many drugs,” he noted.
jury. “Using a proprietary standardized testing yielded no false-positive results, “Hyperbilirubinaemia or gamma-GT in-
generation protocol, these peripheral while RUCAM indicated possible idio- crease per se do not define DILI. While
monocytes are modified to cells with syncratic DILI in six cases. assessment scores and expert opinion
hepatocyte-like properties with do- may be helpful, these are typically un-
nor-specific characteristics, thus allow- “The test can be a future option in able to identify the culprit drug in poly-
ing patient-centric individualized toxicity the diagnosis of complicated idiosyn- medicated patients. Novel in vitro tests
testing,” explained Gerbes. cratic DILI,” Gerbes suggested. are therefore urgently needed to assist
in the diagnosis of idiosyncratic DILI
In a prospective pilot study of 54 “Idiosyncratic DILI can cause acute and in causality assessment in poly-
patients with acute liver injury and in- liver failure in more than 10 percent of medicated patients.”
take of at least one drug, in vitro testing patients, with a transplant-free sur-
using these MH cells identified patients vival rate of approximately 20 percent Idiosyncratic DILI is not as rare as it is
with idiosyncratic DILI with an excellent only,” he continued. [Gut 2009;58:155 believed to be. Its incidence is 14–19 per
sensitivity and a higher specificity than 5-1564; Hepatology 2005;42:481-489] 100,000 population, while that of parac-
the Roussel Uclaf Causality Assess- “It is also a challenge in drug develop- etamol-induced liver injury is 16 per
ment Method (RUCAM) score, the most ment, leading to nonapproval of inno- 100,000 population. Amoxicillin-clavu-
widely used score in the diagnosis of vative drugs, failure in late-stage drug lanate is most commonly implicated in
DILI. [Gut 2016;65:1555-1563] development or postmarketing with- idiosyncratic DILI, accounting for 22 per-
drawal.” cent of the cases, followed by diclofenac
In the study, 31 patients were di- (6 percent), azathioprine (4 percent),
agnosed with idiosyncratic DILI based “Idiosyncratic DILI is very different infliximab (4 percent), and nitrofurantoin
on causality likelihood. MH cell testing from dose-dependent DILI. Its diagno- (4 percent). [Hepatology 2002;36:451-
with the causative drug was positive in sis is difficult because it affects suscep- 455; Pharmacoepidemiol Drug Saf
29 of the patients and was comparable tible patients only and is a diagnosis of 2011;20:819-826; Gastroenterology
to assessment by the RUCAM score. exclusion. It is unpredictable and can 2013;144:1419-1425, 1425.e1-3]
29
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CONFERENCE COVERAGE
TOSCA.IT: Similar CV safety for pioglitazone

and sulphonylureas in T2D
PEARL TOH Additionally, moderate and severe tures (p=0.75), or heart failure (p=0.22).
T
hypoglycaemic events were more com-
he incidence of cardiovascular mon with add-on sulphonylureas than Body weight increase and heart fail-
(CV) events at 5 years was sim- pioglitazone (both p<0.0001). ure rate were lower than those reported
ilar when adding sulphonylureas in previous trials, which the investiga-
or pioglitazone to metformin in patients Although pioglitazone was associ- tors attributed to the exclusion of par-
with type 2 diabetes (T2D) inadequately ated with a better long-term glycaemic ticipants with heart failure (NYHA***
controlled with metformin alone, ac- control, co-investigator Professor Enzo class I or higher) or with reduced renal
cording to a head-to-head comparison Bonora of the University and Hospital function in the current study. [Lancet
in the TOSCA.IT* trial. Trust of Verona, Italy, cautioned that the 2005;366:1279-1289; N Engl J Med
study was done in patients with low CV 2016;374:1321-1331]
“[I]f used appropriately, in terms of disease risk, and that “any extrapola-
patient selection and dose ... both of tion to patients with high CV disease “These low rates [of known side
these widely available and affordable risk for prior events (eg, myocardial in- effects] might be related to the doses
treatments are suitable options with re- farction or stroke) should be avoided.” of drugs used in both groups of the
spect to efficacy and adverse events … trial, which were not maximal, another
particularly in relation to patients with a Other findings and clinical important lesson for clinical practice,”
low CV risk,” wrote the researchers led implications wrote Drs Vivian Fonseca and Dra-
by Dr Olga Vaccaro of the Frederico II The multicentre, prospective, open- gana Lovre of the Tulane University
University of Naples in Naples, Italy. label, blinded endpoint study with a Health Sciences Center in New Orle-
pragmatic design involved 3,028 patients ans, Los Angeles, US, in an accompa-
After a median follow-up of 57.3 aged 50–75 years with T2D who were nying commentary. [Lancet Diabetes
months, similar rates of the composite inadequately controlled on metformin Endocrinol 2017;doi:10.1016/S2213-
primary outcome comprising all-cause monotherapy. They were randomized 8587(17)30320-0]
death, nonfatal stroke, nonfatal myo- 1:1 to add-on pioglitazone 15–45 mg or
cardial infarction, or urgent coronary re- sulphonylureas (gliclazide 30–120 mg [50 “These findings also remind us that pi-
vascularization (7 percent vs 7 percent, percent], glimepiride 2–6 mg [48 percent], oglitazone lowers glucose effectively and
hazard ratio [HR], 0.96; p=0.79) or its or glibenclamide 5–15 mg [2 percent]). durably, and that it is essentially the only
components occurred in both the piogl- available insulin sensitizer that still has a
itazone and sulphonylurea arms, report- Although a moderate weight gain of place in clinical practice,” they added.
ed co-investigator Dr Antonio Nicolucci less than 2 kg occurred in both treat-
of the Center for Outcomes Research ment groups during the first 2 years, “[F]or patients with early diabe-
and Clinical Epidemiology in Pescara, this subsequently levelled off until tes (baseline HbA1c in the TOSCA.IT
Italy. [EASD 2017, session S13; Lancet study end and there were no signifi- trial was 7.7 percent), the choice of a
Diabetes Endocrinol 2017;doi:10.1016/ cant between-group differences. Other second-line drug might not matter as
S2213-8587(17)30317-0] risk factors such as blood pressure, compared with patients who are poor-
eGFR**, albumin-to-creatinine ratio, ly controlled (HbA1c of 9 percent or 10
Glycaemic control was slightly, and C-reactive protein were also simi- percent),” concluded Fonseca and
though significantly, better maintained lar in both treatment groups during the Lovre, calling for head-to-head com-
with add-on pioglitazone than sulpho- course of study. parisons of these drugs with newer
nylureas (mean HbA1c over time, 7.24 antihyperglycaemic drugs in the future.
percent vs 7.30 percent; p=0.01), No significant differences were ob-
with fewer patients in the pioglitazone served between the two groups with re- *TOSCA.IT: Thiazolidinediones Or Sulphonylureas
Cardiovascular Accidents Intervention Trial
arm experiencing treatment failure gards to any type of cancer (specifically **eGFR: Estimated glomerular filtration rate
and needing insulin rescue therapy bladder cancer [p=1.00]), macular oe- ***NYHA: New York Heart Association functional
(p<0.0001 for both). dema (p=0.34), pathological bone frac- classification
30
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CONFERENCE COVERAGE
FAT score predicts poor weight loss

post-RYGB
ELVIRA MANZANO as <28 percent of total weight loss at ducible in the clinic to predict outcomes
A
1-year post-surgery. Poor responders in these patients.”
new score that measures fibro- lost an average 22.7 percent of body
sis in subcutaneous adipose weight whereas good responders lost The FAT score was a significant im-
tissue (scAT) may identify poor 35.6 percent. This translates to an provement of previous attempts to de-
responders to Roux-en-Y gastric by- average difference of 17 kg in weight termine surgical outcomes. However, it
pass (RYGB), a common weight-loss loss between groups. [EASD 2017, ab- can only predict responses in 72 per-
procedure for morbid obesity, a study stract OP-32; J Clin Endocrinol Metab cent of patients, Bel Lassen acknowl-
has shown. 2017;102:2443–2453] edged. “Further refinement is therefore
needed, possibly by including other
Researchers created a fibrosis “The most severe fibrosis scores biological or psychological factors that
score of adipose tissue (FAT score) [greater than 2] presurgery were as- are absent from the current model.”
integrating perilobular and pericellular sociated with a poorer weight-loss re-
fibrosis and tested its predictive value sponse of 3–4 times the risk,” said lead Bel Lassen’s team would also like to
on weight-loss response after RYGB in investigator Dr Pierre Bel Lassen from expand their study to determine if the
183 perioperative scAT biopsy speci- INSERM and Pitié-Salpêtrière Hospital, FAT score can be applied to other types
mens from severely obese patients (85 Assistance Publique– Hôpitaux de Par- of bariatric surgery such as sleeve gas-
from a training cohort and 98 from a is in Paris, France. trectomy, and determine its predictive
confirmation cohort). Mean patient age value over longer follow-up periods.
was 43 years, and average BMI was 47 Factors predicting poor response
kg/m2. Seven out of 10 were women, to RYGB include older age, diabetes, Commenting on the study, Dr Jan
and 39 percent had diabetes. hypertension, and eating disorders, he Eriksson, an endocrinologist from the
said. “[However,] if we pool these pre- Uppsala University in Uppsala, Swe-
At 1 year post-RYGB, the FAT surgery factors, it can only detect 14 den, who is unaffiliated with the study,
score was directly associated with in- percent of post-bariatric weight loss.” said the work had value in finding a
creasing scAT fibrosis (p<0.001). Of measure that could predict who would
note, a FAT score of ≥2 was signifi- Colour detection of collagen in the benefit from RYGB, but it is also inter-
cantly associated with poor response adipose tissue can also predict weight esting from a pathobiology perspec-
to RYGB despite adjusting for pa- loss after surgery, but the procedure tive. “It is surprising that there was an
tient age, diabetes status, high blood is time-consuming, depends on slide increase in the fibrosis score following
pressure, and percentage of body quality, and is affected by heterogeneity the procedure … I would have expect-
fat (adjusted odds ratio [adjOR], 3.6; of fibrosis, he added. “We need a novel, ed the opposite, and this needs further
p=0.003). Poor response was defined easy-to-use score that would be repro- research.”
31
39
CONFERENCE COVERAGE
Comparable glycaemic control

with dulaglutide vs insulin glargine
for T2D patients with CKD
PEARL TOH patients achieving target HbA1c were poglycaemia compared with the insulin
T
similar among the treatment arms at 52 glargine arm (0 percent and 2.6 per-
he GLP-1* receptor agonist du- weeks. cent vs 6.7 percent) at week 26, with
laglutide confers comparable significantly lower hypoglycaemia event
glycaemic control with greater By week 26, albuminuria reductions rate (5.5 and 7.8 vs 17.1 events/par-
albuminuria reduction and less eGFR** occurred in all treatment arms, but the ticipant/year; p<0.001 for both). Also,
decline compared with insulin glargine in extent of reduction was greater in both body weight decreased from baseline
patients with type 2 diabetes (T2D) and the dulaglutide arms compared with the with both dulaglutide doses at 26 and
moderate-to-severe chronic kidney dis- insulin glargine arm (percentage UACR# 52 weeks but increased with insulin
ease (CKD), when both are used in com- change from baseline, -27.7 percent glargine (p<0.001 at both time points).
bination with the human insulin analogue and -26.7 percent vs -16.4 percent).
lispro, according to the AWARD-7*** “Overall there was no significant dif-
study presented at EASD 2017. Commenting on the changes in kid- ference between the insulin and either
ney function in terms of eGFR, Tuttle dose of dulaglutide,” said Tuttle. “The
“The results hold up in CKD stage said, “The eGFR declined at 26 weeks only difference we found was a higher
4, just as it did in CKD [stage] 3, very at about 2 mL/min/1.73m2 in the insu- rate of gastrointestinal side effect in the
similar to what was published in the lin-treated group, note that in patients dulaglutide-treated patients, which was
LEADER trial last week,” said Dr Kath- at this stage of CKD we expect about expected. There was an increase in a
erine Tuttle of the University of Wash- 4-5 mL/min loss, so they were right on dose-related fashion so that the highest
ington in Spokane, Washington, US. target as expected for the insulin group. rates of diarrhoea, nausea, and vomit-
But this was essentially extinguished in ing were observed in the higher-dose
Equivalent reductions in HbA1c lev- the dulaglutide groups where there was dulaglutide group.”
els from baseline at week 26, the pri- no significant loss in eGFR during the
mary endpoint, were seen in both the 26-week time period.”
high- and low-dose dulaglutide arms *GLP-1: Glucagon-like peptide-1
compared with the insulin glargine The open-label phase III trial ran- **eGFR: Estimated glomerular filtration rate
***AWARD-7: A study comparing dulaglutide with
arm (-1.2 percent and -1.1 percent domized 576 patients (mean age 64.6 insulin glargine on glycaemic control in participants
for dulaglutide 1.5 mg and 0.75 mg, years) with T2D and stage 3–4 CKD in with T2D and moderate or severe CKD
respectively, vs -1.1 percent for insulin a 1:1:1 ratio to dulaglutide 1.5 mg or UACR: Urine Albumin-to-Creatinine Ratio
#
glargine; one-sided p<0.001 for nonin- 0.75 mg once weekly or titrated insu-
feriority for both comparisons). [EASD lin glargine, in addition to insulin lispro
2017, abstract OP 02] (adjusted to target preprandial plasma
glucose value of 6.7–10.0 mmol/L).
Likewise, similar proportion of pa-
tients in the dulaglutide arms achieved Previously, dulaglutide 1.5 mg has Scan this QR
code for full
an HbA1c goal of <8.0 percent (<64 demonstrated superiority to daily insu-
coverage of
mmol/mol) as those in the insulin lin glargine in terms of HbA1c change EASD 2017.
glargine arm (78.3 percent and 72.6 from baseline in the AWARD-2 study.
percent vs 75.3 percent). The current AWARD-7 enrolled a spe-
cific group of T2D patients with moder-
“The effects were maintained up ate-to-severe CKD.
to 52 weeks of treatment,” said Tuttle,
noting that the mean HbA1c reduction As expected, fewer participants in
from baseline and the proportion of the dulaglutide arms experienced hy-
32
40
CONFERENCE COVERAGE
Exenatide improves glycaemic control,

weight loss in uncontrolled T2D
O
nce-weekly doses of the glu-
cagon-like peptide-1 receptor
agonist exenatide plus insulin
glargine improved glucose control and
weight loss in patients whose type 2
diabetes (T2D) was uncontrolled on
basal insulin and metformin, according
to findings from the DURATION-7* trial.
“Patients receiving exenatide QW

were twice as likely to have improved
HbA1c and body weight than those
treated with titrated insulin glargine
alone,” said Dr Juan Pablo Frias from
the National Research Institute, Los
Angeles, California, US, who presented
the findings at EASD 2017. placebo (p<0.001), with a more evi- (53.9 percent vs 57.6 percent and 4.7
dent reduction in HbA1c in patients on percent vs 4.8 percent, respectively),
Patients recruited at screening exenatide vs placebo (-1.0 percent vs while more patients on exenatide re-
(n=808) were individuals with uncon- -0.3 percent; least square [LS] mean ported gastrointestinal events (15.1
trolled T2D (HbA1c ≥7.5 to ≤12.0 per- change from baseline, -0.7 percent; percent vs 10.8 percent) and injection
cent; mean HbA1c 9.2 percent) on insu- p<0.001). Patients on exenatide also site-related AEs (7.8 percent vs 3.0
lin glargine (≥20 U/day) with or without experienced a mean 1.1 kg weight loss percent).
metformin and a sulphonylurea. Fol- at 28 weeks compared with patients
lowing an 8-week run-in period during on placebo who gained a mean 0.4 kg Hypoglycaemia incidence was
which insulin glargine was titrated, (LS mean change, -1.5 kg; p<0.001). comparable between patients on exen-
464 patients with HbA1c ≥7.0 to ≤10.5 [EASD 2017, abstract OP 01(3)] atide and placebo (29.7 percent vs 29.0
percent (mean HbA1c, 8.5 percent) de- percent) and there was no incidence of
spite basal insulin and stable metformin Almost 20 percent (19.5 percent) severe hypoglycaemia in either group.
(sulphonylurea use was discontinued) more patients on exenatide than place-
were randomized to receive exenatide bo achieved the composite of reaching “Clinical benefits of combining ex-
once weekly (n=233, mean age 57.8 glycaemic targets with no weight gain enatide QW with basal insulin includ-
years, 49.4 percent male, mean base- or incidence of major hypoglycaemia ed a reduction in HbA1c, with a greater
line weight 93.3 kg) or placebo (n=231, (p<0.001). percentage of patients achieving gly-
mean age 57.6 years, 46.5 percent caemic targets, reduced body weight,
male, mean baseline weight 97.4 kg) A greater proportion of patients and no increase in hypoglycaemia inci-
in addition to titrated insulin glargine on exenatide compared with placebo dence or rate despite improved glycae-
(mean, 50 and 52 U/day in the exen- experienced HbA1c reductions of any mic control,” concluded Frias.
atide and placebo groups, respectively) amount (80.9 percent vs 59.7 percent)
for 28 weeks. as well as any weight loss (62.3 percent
vs 39.8 percent).
At week 28, about 25 percent more *DURATION-7: Phase 3 28-week study with 24-
week and 52-week extension phases to evaluate
patients on exenatide reached the Adverse event (AE) and serious AE efficacy and safety of exenatide once weekly and
target glycaemic goal of HbA1c <7.0 incidence were comparable between dapagliflozin versus exenatide and dapagliflozin
percent compared with patients on patients on exenatide and placebo matching placebo
33
41
CONFERENCE COVERAGE
DS-8500a improves glycaemic, lipid variables

in T2D
AUDREY ABELLA p=0.0233 for 25 mg, -0.34 percent; mg resulted in a significant increase
T
p=0.0004 for 50 mg, and -0.45 per- in HDL cholesterol vs placebo (5.9
he novel G-protein coupled cent; p<0.0001 for 75 mg). percent; p=0.0032 and 6.6 percent;
receptor 119 (GPR119) ago- p=0.0009, respectively), as well as a
nist DS-8500a demonstrated Compared with placebo, DS-8500a significant reduction in total cholesterol
dose-dependent glucose-lowering ef- 50 mg and 75 mg also reduced fast- (-7.0 percent; p<0.0001 and -6.2 per-
fects and favourable improvements in ing plasma glucose (FPG, -12.7 mg/dL; cent; p=0.0002), LDL cholesterol (-7.3
lipid parameters that extended up to 12 p=0.0004 and -14.4 mg/dL; p<0.0001, percent; p=0.0044 and -8.1 percent;
weeks in Japanese patients with type 2 respectively), area under the curve0- p=0.0014), and triglycerides (-32.7
diabetes (T2D), according to data pre- 3h
for glucose during a meal tolerance percent; p<0.0001 and -30.9 percent;
sented at EASD 2017. test (-50.6 mg/dL x h; p=0.0020 and p<0.0001).
-59.7 mg/dL x h; p=0.0003), and
This multicentre, double-blind trial 2-hour postprandial glucose (-18.5 Apart from two cases of clinically
comprised 368 patients with T2D and mg/dL; p=0.0102 and -22.0 mg/dL; relevant drug-related hypoglycaemia in
HbA1c levels between ≥7 and <10 per- p=0.0022). the DS-8500a 50 mg arm, DS-8500a
cent. Participants were randomized was generally well tolerated with no re-
1:1:1 to receive once-daily administra- FPG reduction was sustained for ports of serious drug-related treatment-
tion of DS-8500a (either 25 mg, 50 mg, up to 12 weeks, said the researchers, emergent adverse events at any dose.
or 75 mg), sitagliptin 50 mg, or placebo which is an improvement from other
for 12 weeks. [EASD 2017, abstract 847] GPR119 agonists that typically have These results were consistent with
shorter glucose-lowering effects lasting the findings of a previous study in an-
At week 12, a dose-dependent re- for up to 2–4 weeks only. other Japanese cohort, [Diabetes
duction in HbA1c levels was observed 2016;65:abstract 119-LB] showing the
among patients on DS-8500a com- With regards to lipid profile, admin- potential benefit of DS-8500a for T2D,
pared with placebo (-0.21 percent; istration of DS-8500a 50 mg and 75 noted the researchers.
34
42
CONFERENCE COVERAGE
Ertugliflozin noninferior to glimepiride

in reducing HbA1c
PEARL TOH the ertugliflozin 15 mg arm showing a The double-blind phase III trial ran-
E
significantly greater reduction in fast- domized 1,326 patients with HbA1c
rtugliflozin 15 mg once daily is ing plasma glucose (FPG) through 52 7.0–9.0 percent who were on met-
noninferior to the sulphonylurea weeks from baseline compared with formin ≥1,500 mg/day in a 1:1:1 ratio
glimepiride in HbA1c reduction the glimepiride arm (LS mean, -1.3 vs to ertugliflozin 15 mg or 5 mg, or glime-
over 52 weeks in patients with type 2 -0.9; p<0.001). piride for 52 weeks.
diabetes (T2D) who are inadequately
controlled on metformin, according to Also, significantly greater reduc- In general, similar incidence of
the VERTIS* SU trial presented at EASD tions in body weight were seen with er- drug-related AEs was reported across
2017. tugliflozin vs glimepiride (LS mean, -3.4 treatment groups (21.6 percent and
and -3.0, vs 0.9; p<0.001). 18.3 percent, vs 17.8 percent), with
Along with a lower HbA1c, ertug- comparable rates of AEs leading to
liflozin also resulted in greater body Additional key secondary mea- discontinuation (5.7 percent and 4.0
weight reductions and less hypogly- sure such as systolic blood pressure percent, vs 3.9 percent). Rates of se-
caemia, but more genital mycotic infec- reductions from baseline were greater rious AEs were low (0.7 percent and 0
tions than glimepiride, revealed senior with ertugliflozin than with glimepiride percent, vs 0.2 percent). One and five
investigator Dr Brett Lauring from Ke- through 52 weeks (mean LS, -3.8 and deaths were reported in the ertugliflozin
nilworth, New Jersey, US. -2.2, vs 1.0 mm Hg; p<0.001). 15 mg and 5 mg arms, respectively vs
one death in the glimepiride arm, but
“[Although] sulphonylureas are “Ertugliflozin is an orally adminis- none was considered to be related to
commonly used in patients with T2D tered, potent, highly-selective SGLT2** the study drugs, according to the in-
as second-line therapy … [they] are inhibitor … currently under US and vestigators.
associated with an increased risk of EU regulatory reviews for treatment of
hypoglycaemia and weight gain,” he T2D,” said Lauring. *VERTIS: eValuation of ERTugliplozin efficacy and
continued. “Ertugliflozin improves gly- Safety
caemic control via an insulin-indepen- However, mycotic genital infections **SGLT2: Sodium glucose cotransporter 2
dent mechanism that poses a low risk occurred more frequently in both the
for hypoglycaemia.” ertugliflozin arms than the glimepiride
arm, regardless of gender (female: 10.0
After 52 weeks, ertugliflozin 15 mg percent and 7.7 percent vs 1.4 per-
was noninferior to glimepiride in lower- cent; p<0.001 and p=0.002 for each
Podcast with
ing HbA1c from baseline (least square comparison, and male: 2.1 percent and Dr Bob Ryder
[LS] mean difference, -0.6 vs -0.7). 4.4 percent vs 0 percent; p=0.03 and
Although the lower-dose 5 mg ertug- p=0.002 for each comparison).
liflozin arm also showed similar HbA1c
reduction, this did not reach noninferi- Other prespecified adverse events
ority compared with glimepiride. [EASD (AEs) such as urinary tract infection Podcast with
2017, abstract OP 38] (UTI) and hypovolaemia occurred at Prof Melanie
comparable rates among the treatment Davies
Fewer patients in both the ertug- groups.

liflozin arms than the glimepiride arm
experienced symptomatic hypogly- “Ertugliflozin 5 mg and 15 mg were
caemia (5.2 percent and 3.1 percent, generally well tolerated, without a
vs 19.2 percent for ertugliflozin 15 mg meaningful difference in the incidence
and 5 mg vs glimepiride, respectively; of UTI or hypovolaemia AEs,” observed
p<0.001 for both comparisons), with Lauring.
35
43
NEWSBITES
Higher vitamin E intake may lower risk

of lung cancer
STEPHEN PADILLA
H
igher consumption of dietary
vitamin E provides protection
against lung cancer, according
to a meta-analysis.
“This study is the first meta-analysis

of the dose-response relationship be-
tween dietary vitamin E intake and the
risk of lung cancer,” researchers said.
“Our results indicated that dietary vita-
min E intake was significantly associat-
ed with a reduced risk of lung cancer.”
PubMed and Web of Science were

systematically searched for relevant
studies published from 1955 to April
2015. A random effect model was ap- take and lung cancer risk in mixed pop- reactive radicals. Second, it is capa-
plied to estimate overall relative risks ulation (males and females). Moreover, ble of reducing nitrite and preventing
(RRs) and 95 percent CIs if p<0.05 or an inverse association existed between the production of carcinogenic nitro-
I2 >50 percent; otherwise, a fixed effect dietary vitamin E intake and lung cancer soamides and nitrosoamines. [Free
model was used. risk among current smokers, but not Radic Biol Med 2014;66:3-12; J Im-
among former or never smokers. [Asia munol 2015;195:126-133; J Exp Ther
The funnel plot and Egger’s test Pac J Clin Nutr 2017;26:271-277] Oncol 2012;10:107-112; Toxicology
were used to estimate publication 2002;180:195-207]
bias. The dose-response relationship Analysis by dose response showed
was calculated using the method of that for every 2 mg/d increase in dietary “Additionally, vitamin E may pre-
restricted cubic splines with four knots vitamin E intake, the risk of lung cancer vent carcinogenesis by down regulat-
at percentiles 5, 35, 65 and 95 of the statistically dropped by 5 percent (RR, ing the nuclear factor (NF)-κB signal-
distribution. 0.95; 0.92–0.99; p=0.009 for linearity). ling pathway to inhibit cell proliferation
and angiogenesis, inducing apopto-
The highest dietary vitamin E in- Sensitivity analysis revealed that no sis,” according to researchers. [J Biol
take, compared with the lowest intake, individual study significantly influenced Chem 2007;282:809-820; Eur J Can-
correlated with a reduced risk of lung the pooled effect. In addition, there was cer B Oral Oncol 1996;32B:114-119;
cancer (pooled RR, 0.84; 0.76–0.93; no evidence of publication bias based Ann Med 1991;3:3-12; Science 1983;
I2, 41.1 percent). Based on subgroup on the Egger’s test (t=1.24; p=0.246). 221:1256-1264]
analysis by geographic location, dietary
vitamin E intake was inversely associ- These findings need to be con- The current analysis has several
ated with lung cancer for the European firmed further by larger prospective limitations. First, conclusions should
and American populations (pooled RR, studies, according to researchers, be applied with caution for other re-
0.85; 0.75–0.95), but not for the Asian adding that the inverse relationship be- gions since the included studies were
population. tween dietary vitamin E intake and the limited to America, Europe, and Asia.
risk of lung cancer may be explained by Second, the studies did not report the
No significant association was ob- several mechanisms. association between vitamin E intakes
served between dietary vitamin E in- and different histological types of lung
take and lung cancer risk in males or First, vitamin E is a power antiox- cancer. Thus, researchers could not
females, but there was an inverse rela- idant with anti-inflammatory proper- conduct the stratified analysis by his-
tionship between dietary vitamin E in- ties that protect cells and DNA from tological type.
36
44
NEWSBITES
Tracking change in personality as early indicator

of dementia may be futile
JAIRIA DELA CRUZ
C
hanges in personality traits do
not occur prior to the onset of
mild cognitive impairment (MCI)
or Alzheimer’s disease (AD), a study
has shown.
“The trajectory of personality traits

and facets for individuals who were
later diagnosed with MCI or dementia
did not differ significantly from that of
nonimpaired older adults,” according to
a team of investigators from the Flori-
da State University, Florida, US. “These
findings provide evidence against
the reverse causality hypothesis and
strengthen evidence for personality
traits as a risk factor for dementia.” However, the rate of change in per- in self-rated personality as an early indi-
sonality traits was similar between the cator of dementia is unlikely to be fruit-
Using data from the Baltimore Lon- AD and nonimpaired groups (eg, neu- ful, while a single assessment provides
gitudinal Study of Aging, the investiga- roticism, p=0.91; conscientiousness, reliable information on the personality
tors analysed personality and clinical p=0.24). There was also no evidence of traits that increase resilience [eg, con-
assessments obtained over 36 years accelerated change in personality in the scientiousness] or vulnerability [eg,
from 2,046 community-dwelling older MCI group (eg, neuroticism, p=0.98; neuroticism] to clinical dementia,” they
adults (mean age at first assessment conscientiousness, p=0.18) and all- continued.
62.56 years, 45.5 percent female) with cause dementia group (eg, neuroticism,
no cognitive impairment at baseline. p=0.49; conscientiousness, p=0.07) vs The investigators pointed out that
the nonimpaired group. the lack of evidence suggesting that
All participants completed the neuroticism and conscientiousness
Revised NEO Personality Inventory, a “We further found that personality changed significantly as the onset of
240-item questionnaire evaluating six remained stable even within the last few the disease approached indicates that
facets for each of the five major di- years before the onset of the disease, such traits may confer risk for the de-
mensions: neuroticism, extraversion, and the high rank-order correlations velopment of AD rather than an effect
openness, agreeableness, and con- supported the reliability of the data,” the of disease neuropathology.
scientiousness. investigators said.
The study is not without limitations.
During 24,569 person-years, 104 The differences of approximately Among those that were cited included
(5.1 percent) participants developed 0.3-SD between the AD and nonim- the use of a selective sample with a
MCI and 255 (12.5 percent) were diag- paired groups on the intercept of neu- higher educational level and the rela-
nosed with all-cause dementia, includ- roticism and conscientiousness were tively younger age of nonimpaired par-
ing 194 (9.5 percent) with AD. Partici- said to be not an emerging prodromal ticipants.
pants with dementia scored significantly sign of the disease and were in line with
higher on neuroticism (p<0.001) and results from other prospective studies. “More research is needed on person-
lower on conscientiousness (p<0.001) [Alzheimers Dement 2014;10:179-186; ality and AD biomarkers, and how per-
and extraversion (p=0.02) relative to J Psychiatr Res 2017;89:22-27] sonality may increase resilience against
those without cognitive impairment. neuropathology and forestall the emer-
[JAMA Psychiatry 2017;doi:10.1001/ “From a clinical perspective, these gence of clinical dementia,” the investiga-
jamapsychiatry.2017.2816] findings suggest that tracking change tors said.
38
46
RESEARCH REVIEW
GERD linked to
Music therapy of no
hypertension:
help in autism
Can PPI control both?
G
astro-oesophageal reflux disease (GERD) is correlated
with hypertension, and treatment with a proton pump
inhibitor (PPI) may help to restore oesophageal PH
and control blood pressure (BP), according to a study.
Researchers sought to investigate the impact of 14-day

therapy with omeprazole 20 mg twice daily in patients with
essential hypertension. Patients were monitored of their BP
continuously for 24 hours as well as their pH.
Of 86 essential hypertension patients, 38 had GERD.

There were 494 episodes of pathologic reflux (PR), and 684
episodes of high BP recorded. PR was significantly more
M
common at night time when in supine position (p=0.003).
usic therapy has been shown in previous trials to have
Of the 684 episodes of hypertension, 102 were synchro- positive effects in patients with autism spectrum dis-
nous with PR. GERD patients had significantly higher noctur- order (ASD), but a new study showed it was not the
nal BP than non-GERD patients. There was a correlation in case, contrary to expected results.
the frequencies of high BP and PR episodes in 24-hour period
(p=0.011). In the current study, researchers sought to determine
whether music therapy had long-term benefits in children aged
PPI therapy led to significant reduction in oesophageal 4-7 years with ASD who were naïve to music therapy a year
monitoring parameters (DeMeester score, total duration for prior to study entry. Follow-up was up to 1 year after enrolment.
which pH remained <4, percentage duration for which pH
was <4 in the upright and recumbent positions, number The children were randomly assigned to a control group or
of times pH decreased to <4, number of PR episodes and to a low-intensity, once-weekly music therapy or a high-inten-
PR-dependent BP episodes; p<0.05 for all) and improvement sity (thrice weekly) music therapy. Each music therapy session
in BP parameters (p<0.05 for all). lasted for 30 minutes. The children also received enhanced
standard of care for ASD and were reassessed at 2, 5, and 12
Based on these results, GERD reduction could be used months after randomization.
as an adjunctive therapy for essential hypertension, said the
authors. What is not clear is whether hypertension occurred The primary outcome was a measure of social affect, com-
before or after onset of reflux. paring baseline scores with results after 5 months of intervention.
Li ZT et al. The role of gastroesophageal reflux in provoking high blood pressure

episodes in patients with hypertension. J Clin Gastroenterol 2017;doi: 10.1097/
At the end of the study, both the treatment and control
MCG.0000000000000933. groups had a slight reduction in social affect scores. However,
there was no significant difference in outcome between the mu-
sic therapy and control groups. Improvisational music therapy
added to enhanced standard of care did not provide a benefit
in social affect functioning for children with ASD.
The researchers said the results are very disappointing for

parents and healthcare professionals caring for children with
ASD.
Bieleninik L, et al. Effects of improvisational music therapy versus enhanced

standard care on symptom severity among children with autism spectrum disorder:
the TIME-A randomized clinical trial. JAMA 2017;318:525-535.
39
47
CLINICAL INSIGHTS | IN PRACTICE
Managing diabetes
in primary care
D
iabetes is the 3rd most common abetes in patients who are unaware of
condition attended by GPs in their condition. For some, lifestyle mod-
Singapore polyclinics. The Na- ifications may even alter the course of
tional Health Survey 2010 showed that diabetes, especially during the early
11.3 percent of residents in Singapore phase of the disease.
aged 18–69 years have diabetes.
Dr Teh Ming Ming
Managing diabetes
More recent figure in 2014 showed The key aims of diabetes man-
that about 440,000 residents in Singa- agement are to control blood glucose
pore aged ≥18 years have diabetes. levels to within the normal range and
Vast majority of these cases are type to minimize the risk of developing dia-
2 diabetes (T2D). However, many pa- betes complications. GPs can achieve
tients are unaware that they actually this goal through appropriate use of
have diabetes, necessitating efforts to diabetes pharmacotherapy and em-
raise awareness on the symptoms and powering the patients with knowledge
implications of undiagnosed diabetes. of diabetes management.
Diagnosing diabetes Metformin is the starting point for

Some of the key symptoms of dia- most T2D patients if there is no obvious
betes include frequent urination, exces- contraindication. Dual therapy with the
sive thirst, extreme fatigue, blurred vi- addition of sulphonylureas, dipeptidyl
sion, and slow healing wounds. Missed peptidase-4 inhibitors, thiazolidinedi-
opportunity of detecting diabetes early ones, sodium-glucose cotransporter-2
may lead to complications involving tar- inhibitors, glucagon-like peptide 1 re-
get organ damage such as retinopathy, ceptor agonists, or basal insulin can be
nephropathy, and neuropathy. considered if glycaemic control remains
suboptimum. Triple therapy can be con-
Pearl Toh spoke with Diabetes can be diagnosed when sidered if dual therapy fails to achieve
any one of the following conditions is the optimum glycaemic control.
Dr Teh Ming Ming,
present: random plasma glucose of
senior consultant at the ≥11.1 mmol/L, fasting plasma glucose GPs should consider referring T2D
Department of of ≥7 mmol/L, or plasma glucose of patients to a specialist if triple therapy
Endocrinology, ≥11.1 mmol/L in the 2-hour oral glu- or combination injectable therapy is
Singapore General cose tolerance test. In the event of being considered. Nonetheless, this
Hospital (SGH), on the disagreement between the different di- depends largely on how comfortable
agnostic tests, testing can be repeated. are the GPs in managing complex di-
major challenges of
abetes regimens. On the other hand,
diagnosing and A major challenge in diagnosing di- GPs should consider referring all type 1
managing diabetes abetes is the lack of knowledge on di- diabetes (T1D) patients to a specialist.
in primary care, abetes symptoms at the patient level,
in conjunction with the which could lead to them not seeking For reference, GPs can consult
World Diabetes Day medical help earlier and hence, un- the Ministry of Health Clinical Prac-
derdiagnosis of the disease. tice Guidelines. [Singapore Med J
on 14 November.
2014;55:334-347]
Awareness of the GPs should be vigilant of the risk
symptoms of diabetes is factors of diabetes – such as obesity, Major challenge – hypoglycaemia
important, and patients hypertension, and hyperlipidaemia – One major challenge in diabetes
should be empowered to and encourage patients with these risk treatment lies in striking the right balance
manage their conditions. factors to go for diabetes screening. between achieving the optimum blood
This can facilitate early detection of di- glucose control and minimizing the risk
40
48
CLINICAL INSIGHTS | IN PRACTICE
Particularly, older patients are at a mia due to diminished symptomatic

higher risk of severe hypoglycaemia. responses to hypoglycaemia, termed
This can be potentially devastating as impaired awareness of hypoglycaemia
many older patients may be living alone (IAH). IAH is a significant risk factor for
or spending most part of the day alone. severe hypoglycaemia.
The resulting loss of consciousness
can lead to fall with fractures or signifi- Patients who are at high risk of IAH
cant head injury. include:
(i) T1D patients with tight glycaemic
Therefore, empowering patients control and long duration of dia-
with the basic knowledge of diabetes betes, and
and hypoglycaemia management will (ii) T2D patients with tight glycaemic
complement the efforts of GPs in opti- control.
mizing diabetes control.
Conclusion
What patients can do in managing Pharmacotherapy is only one part
hypoglycaemia of diabetes treatment. Empowering
To avoid hypoglycaemia, patients diabetes patients with the necessary
should follow a regular meal pattern and knowledge and skill in managing diabe-
regularly monitor their blood glucose tes constitutes another important part
levels for those on insulin treatment. of diabetes care. Therefore, GPs should
of hypoglycaemia. Hypoglycaemia oc- Most patients can self-treat hypogly- engage their patients in diabetes care.
curs when blood glucose level falls to <4 caemia by ingestion of carbohydrate
mmol/L. Typical signs and symptoms of or glucose before their blood glucose
hypoglycaemia include tremor, exces- drops to a critical level.
sive sweating, dizziness, palpitation, and Online Resources
double vision, among others. They should also avoid unaccus-
tomed exercise. If the frequency and European Association for the Study
It is important to educate diabetes intensity of exercise is increased, care of Diabetes
patients about the symptoms and im- must be taken by checking blood glu- www.easd.org
plications of hypoglycaemia and to ask cose levels before, during, and after American Diabetes Association
for the occurrence of hypoglycaemia at the exercise such that adjustments of www.diabetes.org
every clinic consultation. When blood diabetes medications or carbohydrate
glucose drops to a very low level, the intake can be made when necessary.
higher executive functions of the brain
will be severely compromised, which What GPs can do in managing
will pose hazards when performing hypoglycaemia
complex task such as driving or oper- Actively looking out for patients with
ating a machine. problematic hypoglycaemia is a good
move to improve diabetes care. There
Scan the
Another important implication re- are some clinical tools which have been
QR code to
lates to self-treatment of hypoglycae- developed to pick up patients with
view more of
mia – the brain is no longer able to problematic hypoglycaemia. One of the
MIMS clinical
make sensible decision on managing user-friendly clinical tools is the Gold
news
hypoglycaemia if the blood glucose questionnaire, which takes less than 10
drops to a critically low level. In the seconds for the patient to complete. A
case of severe hypoglycaemia – which score of ≥4 may indicate problematic
occurs when the patients need help hypoglycaemia.
from others in treating their low blood
glucose levels – this can result in loss of The questionnaire is aimed at pick-
consciousness, seizure or even death if ing up diabetes patients who have a
not intervened in time. reduced ability to detect hypoglycae-
41
49
CALENDAR
NOVEMBER NOVEMBER DECEMBER
17-19
FRIDAY - SUNDAY
23-26
THURSDAY - SUNDAY
02-04
SATURDAY - MONDAY
European Society for Medical 22nd Congress of the ESO-ESMO-RCE Clinical Update
Oncology (ESMO) Asia 2017 Asian Pacific Society of on Rare Adult Solid Cancers
Congress Respirology (APSR) 2017
Location: Singapore Location: Sydney, Australia Location: Milan, Italy
Tel: +41 0 91 973 19 26 Tel: +64 9 360 1240 Fax: +39 0223902531
Email: congress@esmo.org Fax: +64 9 360 1242 Email: raretumours@eso.net
Website: www.esmo.org/Conferences/ES- Email: apsr@tcc.co.nz Website: www.esmo.org/Conferences/ESO-
MO-Asia-2017-Congress Website: www.apsr2017.com ESMO-RCE-Clinical-Update-on-Rare-Adult-
Solid-Cancers-2017
DECEMBER DECEMBER DECEMBER
05-09
TUESDAY - SATURDAY
09-12
SATURDAY - TUESDAY
18-19
MONDAY - TUESDAY
San Antonio Breast Cancer 59th ASH Annual Meeting & 19th International Conference
Symposium (SABCS) 2017 Exposition on Human Genetics (ICHG 2017)
Location: San Antonio, Texas, US Location: Atlanta, Georgia, US Location: Bangkok, Thailand
Tel: 210 450 1550 Tel: 866 828 1231 Website: www.waset.org/confer-
Fax: 210 450 1560 Website: www.hematology.org/Annual-Meet- ence/2017/12/bangkok/ICHG
Email: sabcs@uthscsa.edu ing
Website: www.sabcs.org/2017-SABCS
JANUARY 2018 FEBRUARY 2018 FEBRUARY 2018
18-20
THURSDAY - SATURDAY
05-07
MONDAY - WEDNESDAY
08-10
THURSDAY - SATURDAY
American Society of Clinical ESMO Sarcoma and GIST 2018 Genitourinary Cancers
Oncology (ASCO) 2018 Gastroin- Symposium 2018 Symposium
testinal Cancers Symposium Location: Milan, Italy Location: San Francisco, CA, US
Location: San Francisco, CA, US Tel: +41 0 91 973 19 47 Tel: 888 282 2552; 703 299 0158
Tel: 888 282 2552, 703 299 0158 Fax: +41 0 91 973 19 18 Email: customerservice@asco.org
Fax: 703 299 0255 E-mail: symposia@esmo.org Website: www.gucasym.org
Email: customerservice@asco.org Website: www.esmo.org/Conferences/Sar-
Website: ww.asco.org coma-GIST-2018
42
50

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YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA INDONESIA NOVEMBER 2017

AUSTRALIA • MALAYSIA • HONG KONG

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