medical tribune october 2012 sg

7/28/2019 Medical Tribune October 2012 SG

1/49

October 2012

Short-term uoxene,

venlafaxine ecaciousfor depression

Health policies need to

foster right environment

FORUM DEPRESSION

ESC rolls out new practice guidelines


2/49

1 ring21 pills

vs

Contraceptive Ring or Today's Women

NuvaRing Once-Monthly Convenient

Please read the full prescribing information before prescribing NuvaRing. WOMN-1037663-002208/12

NuvaRing is 99% efective, just like a COC1

Adapted from Ahrendt et al.1

Clinical Ecacy: NuvaRing vs a COC1

(30 mcg of EE and 3 mg of Drospirenone)

NuvaRing (n=499) COC (n=484)

100

0

50

Ecacy,

%

9999

COC: Combined oral contraceptive

EE: Ethinyl Estradiol

0

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60

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NuvaRing (n=499)

COCs (n=484)

Baselin

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Body Weight (mean SD) per Assessment for NuvaRing and COC Groups2

Adapted from Milsom et al. 2COC:Combined oral contraceptive

EE:Ethinyl Estradiol

Weight neutrality2

Reference: 1. Ahrendt H-J, Nisand I, Bastianelli C, et al. Ecacy, acceptability and tolerability o the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 mcg o ethinyl estradiol and 3 mg o drospirenone.Contraception. 2006;74(6):451-457. 2. Milsom I, Lete I, Bjertnaes A, et al. Eects on cycle control an d bodyweight o the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 mcg o ethinyl estradiol and 3 mg o drospirenone.Hum Reprod. 2006;21(9):2304-2311.

Selected Safety InformationContraindications: Presence or history of venous thrombosis or thromboembolic events, with or without pulmonary embolism Presence or history of arterial thrombosis (e.g. cerebrovascular accident, myocardial infarction) or prodromi of a thrombosis (e.g.angina pectoris or transient ischemic attack). Known predisposition or venous or arterial thrombosis, with or without hereditary involvement such as Activated Protein C (APC) resistance, antithrombinIII defciency, protein C defciency, protein S defciency,hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) History of migraine with focal neurological symptoms Diabetes mellitus with vascular involvement The presence of a severe or multiple risk factor(s) for

venous or arterial thrombosis may also constitute a contraindication (see under Special warnings and precautions for use) Pancreatitis or a history thereof if associated with severe hypertriglyceridemia Presence or history of severe hepatic disease as long as liverfunction values have not returned to normal Presence or history of liver tumors (benign or malignant) Known or suspected malignant conditions of the genital organs or the breasts, if sex steroidinuenced Undiagnosed vaginal bleeding Known or suspectedpregnancy Hypersensitivity to the active substances or to any of the excipients of NuvaRing Warnings/Precautions: 1. Circulatory Disorders Epidemiological studies have suggested an association between the use and an increased risk of arterial and venousthrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism These events occur rarely 2. Tumors The most important risk factor for cervical cancer is persistent human papilloma virus (HPV)

infection Epidemiological studies have indicated that longterm use of COCs contributes to this increased risk, but there continues to be uncertainty about the extent to which this nding is attributable to confounding eects, like increased cervical screening anddierence in sexual behavior including use of barrier contraceptives, or a causal association It is unknown how this eect relates to NuvaRing A metaanalysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of havingbreast cancer diagnosed in women who are currently using COCs The excess risk gradually disappears during the course of the 10 years after cessation of COC use Because breast cancer is rare in women under 40 years of age, the excess number of breast cancerdiagnoses in current and recent COC users is small in relation to the overall risk of breast cancer 3. Other conditions: Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs Although small increasesin blood pressure have been reported in many women taking COCs, clinically relevant increases are rare Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal Recurrence ofcholestatic jaundice which occurred rst during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs Diabetic women should be carefully monitored while using NuvaRing especially in the rst months of use Deterioration of Crohns

disease and colitis ulcerosa has been reported in association with the use of hormonal contraceptives Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst using NuvaRing Women who may not be able to insertNuvaRing correctly or may lose the ring if she has prolapse of the uterine cervix, cystocele, and/or rectocele, severe or chronic constipation Women may occasionally experience vaginitis. Adverse Events: Common ( 1/100) includes vaginal infection, depression, libidodecreased, headache, migraine, abdominal pain, nausea, acne, breast tenderness, genital pruritus female, dysmenorrhoea, pelvic pain, vaginal discharge, weight increased, medical device discomfort, vaginal contraceptive device expelled.

MSD Pharma (Singapore) Pte Ltd150 Beach Road #31-00 Gateway West Singapore 189720

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Study Design: A randomized, open-label, multicenter trial (N=983) conducted in 10 European countries. Women were randomized to NuvaRing or a

COC with 30 mcg o EE and 3 mg o drospirenone. Body weight measurements perormed at screening and each study visit were used to estimate the

mean weight change rom baseline within each treatment group and the dierence in weight change in the NuvaRing group vs the COC group.

Study Design: An open-label, randomized, multicenter trial in 10 European countries comparing ecacy, acceptability,

tolerability, and compliance of NuvaRing with a COC containing 30 mcg of EE and 3 mg of drospirenone for 13 cycles (N=983). 1


3/49

3 October 2012

Elvira Manzano

Five new practice guidelines from the

European Society of Cardiology (ESC)

recommend new agents, devices and

therapeutic options for managing valvular

disease, ST segment elevation myocardial

infarction (STEMI), heart failure (HF), atrial

brillation (AF) and cardiovascular disease

(CVD) prevention. A consensus statement

was also issued on the latest universal deni-tion of myocardial infarction (MI).

For valvular disease, the importance of a

collaborative approach between cardiologists

and cardiac surgeons working as a heart

team has been emphasized. For the rst

time, transaortic valve implantation (TAVI) is

recommended in patients with severe symp-

tomatic aortic stenosis (AS) who are unsuit-

able for surgery, but only in hospitals withcardiac surgery on site. TAVI should not be

performed in patients at intermediate risk for

surgery.

Mitral valve repair is the preferred tech-

nique in mitral regurgitation, when the repair

is considered durable. Mitraclip device may

be considered in high-risk or inoperable pa-

tients resistant to optimal medical therapy.

In HF, the key changes from the 2008 ESCguidelines include a new indication for miner-

alocorticoid antagonist (MRA) eplenerone in

patients with systolic HF and mild symptoms,

broadening the indication to essentially all HF-

REF patients remaining symptomatic despite

treatment with a beta-blocker and ACE inhib-

itor or ARB. Ivabradine is now recommended

to be added to an ACE inhibitor, beta-blocker

and MRA for HF-REF patients in sinus rhythm

with a persistently high heart rate (>70 bpm).

The use of cardiac resynchronization thera-

py (CRT) has been expanded to patients with

mild symptoms. Those with a le ventricu-

lar ejection fraction (LVEF) of 35 percent or

lower, sinus rhythm, and le bundle-branch

block QRS morphology, however, benet themost from the device.

The guidelines also recognize the increas-

ing importance of cardiac MRI and include

mid-regional proBNP as a rule-out blood

test in patients with acute HF.

Reperfusion therapy is recommended for

all STEMI patients within 12 hours of rst

symptoms, and beyond the 12-hour window

period if there is persistent pain and ECGchanges. Clopidogrel and aspirin are recom-

mended for brinolysis. Dual antiplatelet

therapy is indicated for up to 12 months in

those having primary PCI, a minimum of 1

month for those receiving a bare metal stent

and 6 months for a drug-eluting stent.

For stroke prevention, the use of CHA2DS2-

VASc score instead of the CHADS2 score is

now recommended for identifying at-risk pa-

tients, and new oral anticoagulants such as

ESC rolls out new practice guidelines

The new guidelines include a range of new options for managing heart

conditions.


4/49

4 October 2012

dabigatran, rivaroxaban or apixaban are now

considered preferable to vitamin K antago-

nists (Class IIA). Dual antiplatelet therapy

with aspirin and clopidogrel, or aspirin only,

may be considered in patients who refuseanticoagulation.

Percutaneous closure of the le atrial

appendage (LAA) may be considered in

those with thromboembolic risk who cannot

be managed with oral anticoagulants in the

long term. Vernakalant has been introduced

as a new antiarrhythmic agent for rapid

cardioversion of recent onset AF, with few

exceptions. The guidelines also highlight the

revised use of dronedarone for paroxysmal or

persistent AF. However, it is contraindicated

in permanent AF and heart failure.

Catheter ablation is advised for patients

with symptomatic paroxysmal AF who have

failed antiarrhythmic medications (Class

IA).

The guidelines on CVD prevention focuson CVD risk, why prevention is needed, and

who should benet from it. CV risks are

classied as very high, high, moderate and

low. Strong recommendations are given on

diet, smoking, hypolipidemic medications,

exercise and other behavioral risk factors.

The ESC also released the latest deni-

tion for ve types of MI and their clinical

implications. The consensus document now

recognizes that small amounts of myocar-

dial injury or necrosis can be detected by

biochemical markers and imaging.

Tai chi can benefit patients with COPD

Elvira Manzano

Amodied tai chi program may im-

prove the exercise capacity and qual-

ity of life of patients with chronic

obstructive pulmonary disease (COPD), new

research has shown.

In a randomized controlled trial, patients

assigned to tai chi were, on average, able towalk 55 meters (95% CI 31 to 80) farther and

384 seconds (95% CI 186 to 510) longer at 12

weeks compared with a control group. [Eur

Respir J2012; DOI:10.1183/09031936.00036912]

An important nding from our study

was the signicant improvement in bal-

ance and muscle strength following Sun-

style tai chi training, which has the poten-

tial to reduce the risk of falls in people withCOPD, said one of the study authors Dr. Tai chi improved muscle strength and balance in study patients.


5/49

5 October 2012

Jennifer Alison, from the University of Sydney,

Australia.

Lower limb muscle weakness and impaired

gait and balance are common in people with

COPD and are major risk factors for falls.In the study, patients were randomized

to a 12-week tai chi program, consisting of a

2-hour session each week, or standard COPD

treatment without exercise. The majority of

the patients were males. Average age was 73,

with co-morbidities that included osteoar-

thritis, hypertension, dyslipidemia and coro-

nary heart disease. On days when patients

were not on sessions, they practiced tai chi at

home for 30 minutes.

Compared with the control group, patients

on tai chi exercise performed 75 percent bet-

ter in the walking test and had a signicantly

higher score in the Chronic Respiratory Dis-

ease Questionnaire, which indicates beer

quality of life.

Additionally, tai chi was associated with

moderate intensity exercise as demonstrated

by a 53-percent reserve in oxygen consump-

tion. Signicant improvements in balance,

strength and performance were also observed

in the tai chi group. The eects of tai chi were

comparable to what can be achieved during

conventional pulmonary rehabilitation.This is good news for people with COPD

because it gives them more tness choices,

said lead study author Ms. Regina Wai Man

Leung of Concord Repatriation General Hos-

pital and the University of Sydney, Austra-

lia. With increasing numbers of people be-

ing diagnosed with COPD, it is important to

provide dierent options for exercise that can

be tailored to suit each individual, added

Leung, a cardiorespiratory physiotherapist.

The authors said the study provides com-

pelling evidence that tai chi may be an eec-

tive alternative training modality for people

with COPD who have limited or no access to

pulmonary rehabilitation. The high degree

of adherence with both formal and at-home

training and practice suggests that the pro-

gram is feasible for COPD patients, even for

those with comorbidities, they concluded.


6/49

6 October 2012 Forum

Health is intrinsically related to

wealth. The Prospective Urban Ru-

ral Epidemiological (PURE) study,a survey of 153,996 adults from 628 urban

and rural communities in 17 countries, has

highlighted the discrepancies in lifestyle

and diet between high-income and low-in-

come nations.

The average fruit and vegetable con-

sumption per day should be 500 grams or

5 servings, but surprisingly, our analysis of

PURE showed that one-third of the coun-tries of the world are not consuming ad-

equate amount. The consumption of fruits

and vegetables increased among nations

with a higher gross domestic product (GDP)

and wealth index, but this was oset by an

increase in the amount of energy obtained

from total and saturated fats, as well as from

protein. Energy from total fat, saturated fats

and protein increased almost linearly withincreasing incomes. Carbohydrate intake,

on the other hand, made up approximately

65 percent of energy from diets in poor na-

tions this is because carbohydrates are a

cheap source of energy with the percent-

age declining in wealthier nations.

Regarding smoking, the decision to

smoke in women depends not only on GDP

or wealth but also on cultural factors, includ-

ing religion. In men, there is a clear inverse

Health policies need to foster right

environment

Excerpted from a presentation by Professor Salim Yusuf, lead researcher of the PURE study

and director of the Population Health Research Institute, McMaster University, Hamilton,

Ontario, Canada, during the 2012 European Society of Cardiology Congress held recently in

Munich, Germany.

relationship between GDP and wealth and

smoking status. Approximately 45 percent

of men in the poorest countries smoke com-

pared with 20 percent of men in the richest

countries. Men started smoking at approxi-

mately the same age and frequency in all

countries, but the rate of quiing is mark-

edly higher in higher-income countries. This

is important because the focus of smokingshould be on quiing. Its the people who

are alive today and who are smoking today

who will die in the next 40 years from to-

bacco. If you can get people to quit, then the

children will not start. This is what we call

epidemiological transition, and this is what

determines risk factors.

In terms of physical activity, the amount

of recreational physical activity increased

with increasing GDP and wealth, but

Recreational exercise alone wont solve the obesity epidemic problem.


7/49

7 October 2012 Forum

this increase was oset by a reduction in

the amount of obligatory physical activ-

ity that is transport-related, job related and

household-related activity required for

physical labor. Overall, the net result was areduction of approximately 2,000 [metabolic

equivalent task] METS/minute/week, or 2.7

hours of brisk walking every day, among

countries with higher incomes.

There is no way unless you are a mar-

athon runner that we are going to over-

come the decrease in activity due to the

changing environment. The obesity epi-

demic really requires a change in environ-

ment. We can yell at people and say, exer-

cise 30 minutes a day. But it is not going

to be enough. Its about one-fourth of the

dierence of lost physical activity whichmeans that in the future, we will all be on

treadmills.

While there are creative solutions, the

key point is to understand that recreational

exercise wont solve the problem and the

entire environment needs to be redesigned.

Thats where policy comes in. We really need

to create the right environment.


8/49

Please visitwww.isrd.org for further details

Nearly 100 Academic Speakers,15 Sessions and 6 Special Topics

ISRD 2012The very first joint scientific sessions

with the American Thoracic Society

English Sessions Highlights

Mechanical Ventilation

Sleep Apnea

Update Biomarkers and Therapeutic Strategiesin Airway Diseases

State-of-the-art Ventilation Strategy

Highlight on COPD Management

ALI Forum - Mechanism and New Drug Target

Plenary Session - Message from ATS

Infection and Immunity

Translational Respiratory Medicine

Congress Secretariat Office

UBM Medica Shanghai

E-mail: [email protected]

Chinese Alliance Against Lung Cancer

(CAALC)

Shanghai Respiratory Research Institute

American Thoracic Society (ATS)

Prof. Monica Kraft

President of AmericanThoracic Society

Professor of Medicine,Vice Chair of Researchfor Department of

Medicine and Directorof the Duke Asthma,Allergy and AirwayCenter at Duke

University MedicalCentre

Prof. Chunxue Bai

President of the 8thISRD & ATS in ChinaForum 2012

Professor of Medicineand Chairman ofDepartment ofPulmonary Medicine,Zhongshan Hospital,Fudan University

Dr. Asrar Malik

Distinguished Professorand Head of theDepartment ofPharmacology,University of IllinoisCollege of Medicine

Schweppe FamillyDistinguished Professorof Pharmacology

Hosted by:

Supported by:

Keynote Speakers:


9/49

9 Singapore FocusOctober 2012

Genes linked to glaucoma

Researchers in Singapore have discovered three genes associated with a type of glaucoma

that is a leading cause of blindness among Chinese people.A genome-wide association study compared 1,854 cases of Primary Angle Closure Glau-

coma (PACG) with 9,608 controls across ve sample collections in Asia and veried the nd-

ings with a further 1,917 PACG cases and 8,943 controls from another six sample collections.

Three new genetic loci were reported to have strong associations with PACG. The disease

occurs when the intraocular pressure builds because the iris bends forward and prevents

uid from draining out of the eye. It aects about 15 million people worldwide, a majority

of whom are Asians.

Our ndings, accumulated across these independent worldwide collections, suggest pos-

sible mechanisms explaining the pathogenesis of PACG, the researchers said.

The research was a collaboration between the Singapore Eye Research Institute, Singa-

pore National Eye Centre, Genome Institute of Singapore, National University of Singapore,

National University Hospitals Department of Ophthalmology and Tan Tock Seng Hospital.

HSA launches clinical trials registry

The Health Sciences Authority (HSA) in Singa-pore recently launched a complete registry ofall clinical trials conducted in Singapore.

The registry will be an easy portal for patients to

nd appropriate clinical trials to join and receive

potentially expensive treatments for lile to no

cost or to seek new treatment options when their

current ones are not working.

The registry may help boost the number of localparticipants in clinical trials, who have oen been

culled from overseas.

It is also an important tool for demonstrating to

pharmaceutical companies that Singapore is an ecient and regulated place to get clinical

trials approved and set up quickly.

The registrys current list includes about 370 trials and the database is sortable by product,

sponsor, trial location and therapeutic area.


10/49


refeences:1. Decramer M. Tiotropium as essential maintenance therapy in COPD. Eur Respir Rev.2006;15:5157. 2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis,Management, and Prevention of Chronic Obstructive Pulmonary Disease.Updated 2010. www.goldcopd.org. Accessed June 24, 2011. 3.Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in

chronic obstructive pulmonary disease. N Engl J Med.2010;363(12):1128-1138 . 4. ODonnell DE, Flge T, Gerken F, et al. Effects of tiotropium on lung hyperination, dyspnoea and exercise tolerance in COPD.Eur Respir J. 2004;23(6):832-840 . 5. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J.2002;19(2):217-224.6. IMS Health Data, Q2 2011. 7. Vogelmeier C, Hederer B, Glaab T, et al; for the POET-COPD Investigators. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med.2011;364(12):1093-1103. 8.Troosters T, Celli B, Lystig T, et al; for the UPLIFT Investigators. Tiotropium as a rst maintenance drug in COPD: secondary analysis of the UPLIFT trial. Eur Respir J. 2010;36(1):65-73.9. Tashkin DP, Celli B, Senn S, et al; for the UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease.N Engl J Med.2008;9(15):1543-1554.10. Data on le. BoehringerIngelheim International GmbH; 2009. 11.Data on le. Boehringer Ingelheim International GmbH; 2011. 12.Tonnel AB, Perez T, Grosbois JM, Verkindre C, Bravo M-L, Brun M; for the TIPHON study group. Effectof tiotropium on health-related quality of life as a primary efcacy endpoint in COPD. Int J Chron Obstruct Pulmon Dis. 2008;3(2):301-310.

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Singaporeans have poor diabetes

self-management

Singaporeans with type 2 diabetes report poor habits and a low level of interest in managingtheir diabetes, according to a survey of 157 local patients.Its complacency and not wanting to know more, said Dr. Kevin Tan Eng Kiat, consultant

endocrinologist and vice president of the Diabetic Society of Singapore. There is the patients own

inertia and doctors not being able to tell them what [metrics] are very important to know.

The survey was carried out at diabetes walk-in centers in 2011. The majority of respondents had

been diagnosed for between 2 and 10 years.

Less than 20 percent of respondents were aware of the key metrics of blood glucose, including

HbA1c, fasting plasma glucose, and postprandial glucose, and what they indicated. Seventy-sixpercent of respondents were not sure or not interested to know more about these measurements.

We have to educate doctors that these are important things patients should know, Tan said.

The survey was a joint eort between the Diabetic Society of Singapore, AstraZeneca and

Bristol-Myers Squibb.


11/49


Rajesh Kumar

Anewly established expert panel on os-

teoarthritis (OA) is intended as an ed-

ucational resource for Singapore GPs.

The panel, comprising a sports medicine

physician, an orthopaedic surgeon, a rheuma-

tologist and a GP specializing in OA, is orga-

nizing a series of training workshops to helpGPs refresh their knowledge base and exper-

tise on the subject.

Two upcoming training sessions are

planned for 20 October at Singapore General

Hospital (SGH) and 23 November at Changi

General Hospital (CGH).

The panel members will also act as expert

media commentators on OA to raise public

awareness on the importance of early detec-

tion and various treatment options.

OA aects an estimated 40 percent of Sin-

gaporeans at some stage of their lives and, ac-cording to SingHealth, only about 10 percent

seek treatment.

We all experience aches and pains but pa-

tients sometimes dont realize that it could be

something more serious. So they dont discuss

it with their primary healthcare physician,

said Dr. Darryl Chew, GP at the E Medical

Clinic and a member of the expert panel.

The lack of awareness among patients

could be one very real reason why OA can go

undiagnosed, and unfortunately untreated,

until the disease further progresses to a much

worse severity.

OA is common among the elderly over

70 years of age due to gradual deteriora-

tion of joint cartilage. Young people who are

active in high-impact sports are also at high-

er risk due to meniscus damage sustained

from sports injuries.But young patients think knee OA cant af-

fect them. In case of aches and pains, they

apply ice packs and muscle creams, and take

NSAIDs thinking it will go away in time.

This delays their diagnosis and worsens the

symptoms, said Chew.

Early detection can not only help slow

disease progression, but may also delay the

need for the most aggressive interventionssuch as joint replacement surgery.

NSAIDs, surgery and physical therapy

are the most commonly prescribed treat-

ments, but the expert panel plans to also

raise awareness about viscosupplementation

which helps delay disease progression and

manage chronic pain.

Obesity, a sedentary lifestyle, genetics and

improper exercise techniques are among themain culprits, which need to be adequate-

ly addressed for a long term resolution of

patients pain and suering.

Other members of the panel include Dr.

Benedict Tan, sports medicine physician

at CGH, Dr. Darren Tay, orthopaedic sur-

geon at SGH, Dr. Carol Tan, geriatrician at

Raes Hospital, and Dr. Yoon Kam Hon,

rheumatologist at the Arthritis and Rheuma-

tism Specialist Medical Centre.

Osteoarthritis training workshops

target GPs

We all experience aches and pains but

patients sometimes dont realize that

it could be something more serious


12/49


Knowledge gaps in Asian women on fertility

Rajesh Kumar

Arecent study of 1,000 women across 10Asian countries, including Singapore,has highlighted critical knowledge gaps on

fertility, main causes of infertility and treat-

ment options.

Only 36 percent of the women surveyed,

all under 35 who were trying to conceive for

at least 6 months, understood that women

generally have a lower chance of geingpregnant in their 40s, compared with their

30s. Also, only 43 percent knew that a couple

is classied as infertile if they fail to conceive

aer 1 year of trying, while 32 percent knew

that a healthy lifestyle does not necessarily

guarantee fertility.

Researchers also noticed a widespread

lack of knowledge about male fertility is-

sues around 40 percent of women did notknow that a man may be infertile even if he

can achieve an erection and produce sperm.

The Starting Families Asia study was com-

missioned by Merck Serono in collaboration

with Professor PC. Wong, senior consultant

and head of the division of reproductive en-

docrinology and infertility at the National

University Hospital Womens Centre.

The results could be indicative of thepotential barriers to the help that women

and couples should be seeking and receiving

when planning to start a family, especiallyfor those facing diculty in conceiving,

said Wong.

These results also highlight the need for

more public education and awareness on the

impact of age and medical problems on fer-

tility, as well as the infertility treatment op-

tions available, he added.

Many women believed that fate plays a

part in fertility problems. In Singapore, 59percent of women believed that infertility

is Gods will and 42 percent aributed it

to bad luck. The single greatest barrier

to seeking help in Singapore, Korea, Hong

Kong and Taiwan is the perceived high cost

associated with fertility treatment, although

the Singapore government subsidizes up to

three IVF cycles.

Asian countries have among the lowestfertility rates in the world and the declining

birth rates are a cause for concern. Merck

Serono commissioned the study to beer

understand Asian womens decision-making

considerations around having a baby. In-

sights from this study will (hopefully) assist

healthcare professionals and policy makers

in addressing this acute challenge, said Mr.

Tim Kneen, Merck Serono regional vice-president for Asia Pacic.


13/49


HPB launches health choices toolkit for GPs

Rajesh Kumar

The Health Choices Toolkit launched bythe Health Promotion Board (HPB) aimsto equip GPs and other healthcare profession-

als with the necessary tools to improve their

patients health literacy and help modify their

lifestyle risk factors for chronic diseases.

Focusing on smoking, obesity, stress and

unsafe sexual practices, the kit consists of a

practice manual, a tabletop ip chart for useduring patient consultation, a poster and in-

formation brochures to prompt patients to

start or continue conversations about their

lifestyle habits and a dedicated webpage for

viewing case videos and downloading re-

sources.

A Physical Activity Advice Tool (PAAT) is

also included to help physicians assess their

patients quickly, give brief advice and pro-vide tailored counseling. PAAT takes the 3As

brief approach (Ask, Advise and Action) as

well as the 5As intensive approach (Ask, Ad-

vise, Assess, Assist and Arrange) to counsel-

ing and provides clear steps for conducting

guided dialogue with patients about making

lifestyle changes.

Studies show that people who are un-

well are more likely to make healthy lifestyle

changes recommended by their doctors, saidHPB chief executive Mr. Ang Hak Seng.

The toolkit was developed as a convenient

and user-friendly tool in Singapores four lan-

guages to help healthcare professionals pro-

actively give tailored evidence-based health

advice to patients who are at risk of develop-

ing or mismanaging chronic conditions.

It takes into consideration the fact that

busy healthcare professionals have limitedcapacity and time, and is therefore designed

to enable them to assess patients quickly and

give brief but eective advice, said Ang.

HPB is organizing a national conference to

share best practices with all health profession-

als and will conduct capacity building cours-

es for them. By October-end, it also plans to

sign Memorandums of Understanding with

the Singapore Physiotherapy Association,Pharmaceutical Society of Singapore, and Sin-

gapore Association of Occupational Thera-

pists for the development of a health promot-

ing curriculum, engagement of allied health

professionals in providing eective health

advice and intervention and their mobilization

during HPBs outreach eorts to raise health

literacy.

Rajesh Kumar

GPs in Singapore and the neighboring re-gions of Johor Bahru, Batam and Bintanare being urged to quickly identify and re-fer patients with dengue fever to SingHealth

for testing the ecacy of a drug against thedisease.

The double-blind, randomized, placebo-controlled proof-of-concept CELADEN*

trial is testing whether celegosivir lowers theamount of viremia and diminishes fever and

Dengue drug trial seeks patients


14/49


pain to a greater extent, compared with pa-tients who receive standard care involvinguids and paracetamol.

Patients must have conrmed dengue fe-

ver of less than 48 hours, be in generally goodhealth, and not be taking blood thinners orhave a history of gastrointestinal disorders,said project manager associate professor Cyn-thia Sung of the program in emerging infec-tious diseases at Duke-NUS Graduate Medi-cal School, Singapore.

Dengue can be conrmed with a simpleblood test that takes 10-15 minutes to get the

result. Free diagnostic test kits are being madeavailable to GPs who choose to be a part of thetrial.

GPs are the rst line of health care pro-fessionals who patients contact when they getdengue, said Sung.

The only way to know if celgosivir is anactive drug is to study its eects on peoplewho have dengue fever. It would be a worldrst if we can show activity.

At least 50 patients with conrmed denguewill be required to stay at the investigationalmedicine unit at Singapore General Hospitalfor 5 days and will need to return for 3 shortoutpatient visits the following week. The re-searchers will monitor their blood counts, he-matocrit, drug concentrations, and immuno-logical status. All medical care and treatmentis free, and patients will receive a generous

cash payment.Our challenge is to let the GP communi-ties know the importance of geing patientstested early in the course of disease to deter-mine if they suspect dengue, Sung added.

The symptoms of dengue are sudden on-set of fever, headache, retro-orbital pain andmuscle and joint pain. Symptoms such as wa-tery eyes, nasal congestion or cough typicallyassociated with common inuenza or cough

and cold are absent in dengue, which couldmake it easier to distinguish.

Two other drugs have been tested againstdengue chloroquine in Brazil and balapira-vir in Vietnam. But neither has shown ecacyagainst the endemic tropical disease.

The Sano-Pasteur tetravalent vaccine thatwas trialed recently showed only 30 percentecacy, dashing hopes for a viable vaccine inthe immediate future. But vaccines are used

as a preventative measure and are not usefulaer a patient has contracted an acute diseaselike dengue. That leaves celegosivir as theonly potential antiviral solution for denguefor the time being, said Sung.

CELADEN is funded by the STOP Den-gue consortium, from a National MedicalResearch Council grant. GPs can check outwww.celaden.sg or call dengue hotline: +65-8155 6283 / 6293 for more details.

*CELADEN: Celegosivir as a treatment against dengue

Selected patients will receive medical care and treatment for free.


15/49


Genotyping can help avoid SJS/TEN in

epileptic patients

Rajesh Kumar

Asian patients with a particular genetic traithave a higher risk of developing Stevens-Johnson syndrome (SJS) and toxic epidermal

necrolysis (TEN) when treated with the anti-

epileptic drugs carbamazepine and phenytoin.

But genotyping for human leukocyte agent

variant (HLA)-B*1502 allele and providingmore expensive alternate anti-epileptic drugs

to those who test positive is cost-eective for

Singaporean Chinese and Malays, but not for

Singaporean Indians, a local research has re-

vealed.

The researchers used patient data to develop

a statistical model that took into account costs

of epilepsy treatments and genotyping, reduc-

tions in quality of life and increased costs re-

sulting from SJS/TEN complications, the prev-

alence of the risk allele, the positive predictive

value (PPV) of genotyping, life expectancy, and

other factors. [Neurology 2012; 79:1259-1267]

The options were treatment with carbam-

azepine or phenytoin without genotyping or

providing more expensive drugs that do not

induce SJS/TEN to all patients without geno-

typing.

Compared with no genotyping and provid-

ing carbamazepine to all, genotyping at the

cost of $205 per patient results in an incremen-

tal cost-eectiveness ratio of $38,620/quality-

adjusted life year (QALY) for Chinese patients,

$8,420/QALY for Malays, and $122,530/QALY

for Indians in Singapore, said researcher Ms.

Dong Di of the Duke-NUS Graduate Medi-

cal School, Singapore. Lower amount denotes

higher cost-eectiveness.

With an odds ratio of 1,357, PPV of 5.6 per-

cent and negative predictive value of 99.9 per-

cent, the HLA-B*1502 testing can have appli-

cations for the Han Chinese, Malaysians and

south Indians in other countries. The allele is

absent among US Caucasians, Hispanics, na-

tive Americans and Africans, but has 5 percent

to 27 percent prevalence in the Han Chinese,

Malays, Thais, Filipinos and Vietnamese.

However, the absence of this allele in other

groups does not mean they cannot develop

SJS/TEN, cautioned Associate Professor Eric A.

Finkelstein, deputy director of the Health Servic-

es & Systems Research Program at Duke-NUS.

Also, lack of cost-eectiveness is no reason

to not oer targeted therapy to low-risk Singa-

porean Indians who could potentially pay for

higher treatment costs to avoid SJS/TEN alto-

gether, said Finkelstein.

Carbamazepine and phenytoin are also

used for trigeminal neuralgia, bipolar

disorders and other neurological conditions

and the same evidence on cost eectiveness

can guide treatment decisions in those Asian

patients.

Genotyping is cost-eective for Singaporean Chinese and Malays


16/49


Extended-release metformin makes dosing

easier

Radha Chitale

An extended-release version of metforminreduces the number of medication dosestype 2 diabetes patients need to take each day.

The formulation, a combination therapy

with the DPP-4 inhibitor saxagliptin is now

available in Singapore and should be on the

market within a few months.This is the rst and only xed dose com-

bination that can be dosed once a day, said

Dr. Nancy Bohannon, director of Clinical Re-

search at the Cardiovascular Risk Reduction

Program at St. Lukes Hospital in San Fran-

cisco, California, US. That really improves

the compliance to the medication.

The proportion of Singaporeans with dia-

betes increased from 8.2 percent in 2004 to11.3 percent in 2010, according the 2011 Na-

tional Registry of Diseases. Almost half of

Singaporeans with diabetes are unaware they

have the disease.

Current international guidelines recom-

mend metformin monotherapy plus diet con-

trol and increased exercise as initial therapy.

However, if the blood sugar indicator HbA1c

level is above 7.6 percent, combination thera-

py (metformin plus a DPP-4 inhibitor) is rec-

ommended as rst line therapy in addition to

lifestyle changes. [Diabetes Care 2009;32:193-

203; Endocr Pract 2009;15:540-559]

A 2009 trial comparing metformin plus

saxagliptin with metformin plus placebo in

treatment-naive diabetic patients demon-strated an HbA1c reduction of 2 percent with

metformin alone and 2.5 percent with metfor-

min/saxagliptin combination therapy. [Diabe-

tes Obes Metab 2009;11:611-622]

The results showed that 60 percent of pa-

tients reached target HbA1c levels (


17/49


from the National Cancer Centre Singapore

(NCCS). Even more worrying is that approx-

imately 20 percent of patients present in an

advanced stage.

Tan said the increase is partly due to in-creased detection of tumors on computed to-

mography (CT) scans. More cases are being

picked up at early stages. Tumors as small as

3-5 cm that might have gone unnoticed, or

cannot be palpated by physicians just like in

breast cancer, can be detected by the scan. As

a result, doctors are now seeing more cases of

kidney cancer about 160 to 200 cases a year

compared with 60 to 70 cases in 1997.

Rising obesity rates and smoking are the

two other most common reversible factors

that contribute to the increase, Tan said. A

healthy weight and smoking prevention can

therefore cut the risk.

Other risk factors are age, gender, family

history, hypertension, long-term dialysis and

genetic syndromes. Incidence rates peak be-

tween 60 to 70 years of age. Men have 1.5 times

higher risk than women. Once metastatic dis-

ease develops, 5-year survival is from 0 to 20

percent, and half of patients undergoing cura-

tive surgery are likely to experience relapse at

distant sites.

Kidney cancer is unpredictable, however

there are new therapeutic options available

for patients, said Dr. Tay Miah Hang, consul-tant medical oncologist at OncoCare Cancer

Centre, Singapore. Renal cell carcinoma, al-

though highly resistant to radiotherapy and

chemotherapy, can be treated. Life expectancy

can be prolonged and complications arising

from disease progression can be reduced.

Pazopanib, the sixth targeted therapy ap-

proved for the treatment of advanced kidney

cancer, blocks the growth of new blood ves-

sels needed for tumor development. In a study

involving 435 patients with advanced kidney

cancer, treatment with pazopanib achieved

median progression-free survival (PFS) of

9.2 months vs. 4.2 months for placebo (HR

0.46, P


18/49


16/10/12

GP-CME Management of Diabetic

NephropathyInfo : National Healthcare Group (NHG) Polyclinics

Tel : +65 6896 2071

Website : http://www.nhg.com.sg/events.asp?eventgroup=4

16/10/12

GP-CME Updates in COPD ManagementInfo : National Healthcare Group (NHG) Polyclinics

Tel : +65 6355 3000


17/10/12

GP-CME Early Intervention in PsychosisInfo : National Healthcare Group (NHG) Polyclinics

Tel : +65 6353 2461


17/10/12

GP-CME Updates in COPD ManagementInfo : National Healthcare Group (NHG) Polyclinics

Tel : +65 6554 7469


Singapore Events18/10/12

GP-CME Constipation in the Elderly

Info : National Healthcare Group (NHG) PolyclinicsTel : +65 6355 3000


19/10/12

GP-CME Management & Referrals of CommonSkin ConditionsInfo : National Healthcare Group (NHG) Polyclinics

Tel : +65 6355 3000


23/11/12

GP Workshop Knee Osteoarthritis/

Viscosupplementation InjectorLocation : St Andrews Community Hospital, Seminar

Room, Level 2

Time : 1:00 PM to 4:30 PM

RSVP : [email protected] by 9/11/12


19/49

19 October 2012 Conference CoverageEuropean Society of Cardiology Congress, 25-29 August, Munich, Germany

Aspirin can be dropped in PCI patients on

oral anticoagulantsChristina Lau

Patients on oral anticoagulants (OAC)

undergoing percutaneous coronary in-

tervention (PCI) should be treated with

clopidogrel, but not aspirin, according to the rst

randomized trial to assess optimal antithrom-

botic therapy in this high-risk group of patients.The trial showed that dual therapy with OAC

and clopidogrel causes less bleeding than triple

therapy with OAC, aspirin and clopidogrel, and

is safe with respect to preventing thrombotic and

thromboembolic complications.

Long-term OAC therapy is obligatory in

most patients with atrial brillation (AF) and

in those with mechanical heart valves. Over 30

percent of these patients have concomitant isch-emic heart disease and, if they need to undergo

PCI, aspirin and clopidogrel are indicated, said

lead investigator Professor Willem Dewilde of

the TweeSteden Hospital in Tilburg, the Nether-

lands.

Until now, no prospective randomized data

were available on the optimal antithrombotic

therapy for these patients, he continued. Al-

though triple therapy seems logical for the pre-vention of stroke and stent thrombosis, it oen

causes serious bleeding complications and the

need to discontinue aspirin and clopidogrel.

The WOEST* study included 573 patients

from the Netherlands and Belgium, who were

already on OAC for AF or mechanical valves and

were undergoing PCI. The primary endpoint

was occurrence of all bleeding events aer 1 year,

classied according to the TIMI (Thrombosis in

Myocardial Infarction) bleeding criteria. Second-

ary endpoints were the combination of stroke,

death, MI, stent thrombosis and target vessel re-

vascularization, and all individual components

of the primary and secondary endpoints.

At 1 year aer PCI, patients in the dual ther-

apy group had signicantly lower incidence

of bleeding (19.5 vss 44.9 percent; HR=0.36;

P


20/49

20 October 2012 Conference Coverage

Investigational drug shows promise in HF

Christina Lau

Anovel angiotensin receptor ne-

prilysin inhibitor LCZ696 has

demonstrated benecial eects in

heart failure (HF) patients with preserved

ejection fraction in a phase II trial.

LCZ696 is a rst-in-class agent

comprising the molecular moieties of a

neprilysin inhibitor and the angiotensin

receptor inhibitor (ARB) valsartan as asingle compound. Its dual mechanism of

action is believed to restore the altered

neurohormonal balance in HF with

preserved ejection fraction.

In the PARAMOUNT* study, the ecacy

and safety of LCZ696 was compared with

that of valsartan in 308 patients from 13

countries. [Lancet 2012; DOI:10.1016/S0140-

6736(12)61227-6]HF with preserved ejection fraction

accounts for up to half of HF cases, and is

associated with substantial morbidity and

mortality. However, no therapies have

been shown to improve clinical outcomes

in this condition, said lead investigator

Professor Sco Solomon of the Harvard

Medical School and the Brigham and

Womens Hospital in Boston, Massachuses,US.

Results showed that aer 12 weeks of

therapy, LCZ696 signicantly reduced

levels of NT-probBNP by 23 percent

compared with valsartan (P=0.005). NT-

proBNP is a marker of cardiac wall stress,

and levels are increased in HF patients,

explained Solomon. The greater reduc-

tion in NT-proBNP achieved with LCZ696

was sustained to 36 weeks, although the

dierence vs. valsartan was no longer

signicant.Patients treated with LCZ696 also had

reduced le atrial size and improved

symptoms (as measured by New York Heart

Association [NYHA] Functional Classica-

tion), both of which became signicant vs.

valsartan by week 36.

LCZ696 was generally well tolerated,

with fewer serious and overall adverse

events than valsartan, said Solomon.Results from PARAMOUNT are encourag-

ing, and LCZ696 is currently being tested

in a trial of 8,000 HF patients with reduced

ejection fraction.

In another study, spironolactone was

shown to improve cardiac function and

structure, and reduce neuroendocrine

activation in 422 patients with symptomatic

diastolic HF.In the international phase IIb Aldo-

DHF trial, 12-month treatment with the

aldosterone receptor antagonist improved

diastolic function, induced structural reverse

remodeling, and reduced NT-proBNP levels

and blood pressure compared with place-

bo, reported Professor Burkert Pieske of the

Medical University of Graz in Austria. How-

ever, the treatment did not improve exercisecapacity, NYHA class or quality of life.

Spironolactone was shown to be safe, with-

out severe adverse events. The drug can be

considered in patients with diastolic HF, for

improving cardiac function and blood pres-

sure control, suggested Pieske.

*PARAMOUNT = Prospective compArison of ARNI with ARB on

Management Of heart fai lUre with preserved ejectioN fraction

**Aldo-DHF = Aldosterone Receptor Blockade in Diastolic Heart Failure


21/49


Niacin/laropiprant well tolerated in

HPS2-THRIVE trial

Alexandra Kirsten

More than three-quarters of patients

taking long-term extended release

niacin/laropiprant (ERN/LRPT)

in the HPS2-THRIVE* trial have tolerated

treatment, according to preliminary results.

HPS2-THRIVE is the largest study so far

to assess whether adding ERN/LRPT to statintherapy can further lower cardiovascular risk.

In the trial, a total of 25,673 patients

with occlusive arterial vascular disease

from the UK, Scandinavia and China were

randomized to receive long-term treatment

with either ERN/LRPT 2 mg or placebo, in

addition to simvastatin therapy. The primary

endpoint included major vascular events aer a

median follow-up of 4 years.The preliminary results suggest that

about 76 percent of the patients can tolerate

long-term ERN/LRPT treatment.

A safety analysis suggested that myopathy

occurred in 0.5 percent of patients treated with

simvastatin 40 mg and ERN/LRPT, however,

the vast majority of these cases were found in

patients with Chinese descent.

These observations have resulted in a

label change for simvastatin and ERN/LRPT,

explained lead study author Professor JaneArmitage, consultant in Public Health

Medicine at the University of Oxford, England,

adding that patients of Chinese descent should not

receive simvastatin 80 mg with cholesterol-

modifying doses of niacin-containing products.

Niacin did not show any clear adverse eects

on the liver in the trial, but known cutaneous

and gastrointestinal side eects were conrmed.

Niacin has been shown to be an eec-

tive HDL-raising agent, but randomized trial

evidence for benecial cardiovascular eects

is limited. Most previous studies have been

performed using brates, which raise HDL

cholesterol only modestly, and those studies

produced mixed results. Moreover, the tolera-

bility of niacin has been limited by ushing andcutaneous side-eects, which appear to be

mediated largely by prostaglandin D. These

side eects can be substantially reduced by

laropiprant, a selective prostaglandin D

receptor antagonist.

Further results from the HPS2-THRIVE are

expected to be released in 2013.

*HPS2-THRIVE: Heart Protection Study 2 -Treatment of HDL to Reduce the

Incidence of Vascular Events

Niacin has been shown to be an eective HDL-raising agent.

The preliminary results

suggest that about 76 percent

of the patients can tolerate long-term ERN/

LRPT treatment


22/49

22 October 2012 Conference CoverageEuropean Society of Cardiology Congress, 25-29 August, Munich, Germany

Aliskiren use not advised in type 2 diabetics

with renal impairmentAlexandra Kirsten

Aliskiren, a direct renin inhibitor,

should not be used to lower blood

pressure in type 2 diabetics at high

risk of cardiovascular and renal events, ac-

cording the ndings of the Aliskiren Trial inType 2 Diabetes Using Cardio-Renal End-

points (ALTITUDE).

The treatment may even be harmful in

these patients, said lead study author Profes-

sor Hans-Henrik Parving from the University

of Copenhagen, Denmark

In the ALTITUDE study, a total of 8,561 pa-

tients with type 2 diabetes and renal impair-

ment were randomized to double-blind treat-ment with either aliskerin 300 mg or placebo

once daily, in addition to an angiotensin co-

verting enzyme (ACE) inhibitor or angioten-

sin receptor blocker (ARB).

The primary analysis was the time to the

rst event for the composite endpoint of

cardiovascular death, resuscitated death,

non-fatal myocardial infarction and stroke,

unplanned hospitalization for heart failure,onset of end-stage renal disease or doubling

of baseline creatinine.

Aer the monitoring commiee found an

increased rate of side eects associated with

active treatment, the trial was stopped prema-

turely.

At a median follow-up of 32 months, the

primary endpoint had occurred in 767 pa-

tients taking aliskiren (17.9 percent) and in

721 assigned to placebo (16.8 percent) [95%

CI 0.98-1.20, P=0.14]. Corresponding rates of

stroke in each group were 3.4 percent and

2.7 percent, respectively (95% CI 0.98-1.60,

P=0.070).

Laboratory results showed albuminuria

levels to be 14 percent lower in aliskiren-treated patients, while increases in serum

creatinine appeared similar in the two groups.

Patients in the aliskiren group experienced

signicantly increased serum potassium

levels of 6 mmol/L (8.8 percent vs. 5.6 percent

for placebo), and higher rates of hypotension

(12.1 percent vs. 8.0 percent, respectively).

These results do not support the admin-

istration of aliskiren on top of standard ther-apy in type 2 diabetic patients at high risk for

cardiovascular and renal events, concluded

Parving.

Aliskiren is the rst in the class of drugs

called direct renin inhibitors. It was approved

in 2007 in the EU and US under the brand-

names Rasilez and Tekturna, respectively, for

the treatment of essential (primary) hyperten-

sion either as monotherapy or in combination

with other medications.

Aliskiren may do more harm than good in type 2 diabetics with renal

problems.


23/49

ACE inhibitors versus ARBs:

Myths and Facts

Professor Frank RuschitzkaHeart Failure/Transplantation ClinicUniversity Clinic ZurichSwitzerland

The pathophysiology o hypertension involves severalactors and its management necessitates an individu-alised approach; with treatments tailored to an indi-

viduals patient prole. International consensus guide-lines recommend the stratication o cardiovascularrisk o individual patients to quantiy prognosis as wellas to determine an optimal treatment approach basedon individual risk prole. For example a patient withGrade 1 hypertension (SBP: 140-159; DBP: 90-99)with no other additional risk actors would be advisedto make liestyle changes or several months beorea drug treatment was initiated. However, a patienthaving similar Grade 1 hypertension with concurrentpresence o three or more risk actors or diabeteswould require immediate drug treatment and inten-sive liestyle changes.

The evidence underscores thathypertension cannot be treated inisolation as just blood pressure. It

is part of the whole cardiovascularcontinuum and the ultimate

treatment goal should be to reduceoverall morbidity and mortality

Role of RAAS targeted therapy in the

management of hypertension

Angiotensin II plays a central role in organ damage;treatment o hypertension should thus ocus onreducing angiotensin levels. ACE inhibitors andangiotensin receptor blockers (ARB) are the twomain drug classes that act on the RAAS. However,while ACE inhibitors reduce angiotensin II levelsand increase bradykinin; ARBs have an antagonistaction only on AT1 receptors, one o the our types oangiotensin receptors present.

Moreover, receptor blockade by anARB conversely triggers substantialincrease in angiotensin II levels

The benets o ACE inhibitor therapy in reducing car-diovascular risks was demonstrated in the EUROPA,wherein 12,218 patients with stable coronary arterydisease and no apparent heart ailure were randomizedto receive an ACE inhibitor perindopril or a matchingplacebo. Ater a mean ollow-up period o 4.2 years,treatment with perindopril was ound to coner a 20%relative risk reduction in cardiovascular death, myocar-dial inarction, or cardiac arrest.1 This has been urthercorroborated in a meta-analysis o ACE inhibitor trialsin coronary artery disease patients without heart ailure

or let ventricular dysunction, which reported a signi-cant reduction o 14% in all cause mortality, 19% incardiovascular mortality, 18% in myocardial inarction,and a 23% reduction in stroke.2 In addition, there wasa 42% reduction in cardiac arrest, an 8% reductionin myocardial revascularization and a 24% reductionin hospitalization or heart ailure with ACE inhibitorbased treatment.2

Preferred combination approach to

hypertension management

Since several mechanisms are involved in the patho-

genesis o hypertension; most patients require com-bination therapy to ensure optimal blood pressurecontrol. Due to their complementary modes o action,ACE-inhibitors and calcium antagonists are the combi-nation therapy o rst choice.3 This was demonstratedin the ASCOT-BPLA, a multicentre randomized con-trolled trial in 19,257 patients with hypertension and atleast three other cardiovascular risk actors who wererandomised to amlodipine plus perindopril or atenololand bendrofumethiazide based therapy. Following 5.5years ollow up, patients on the perindopril and am-lodipine combination reported signicantly ewer ataland non-atal stroke (P=0.0003), total cardiovascularevents and procedures (P


24/49


European Respiratory Society Annual Congress, 1-5 September, Vienna, Austria

Long-distance running raises pulmonary

edema risk

Half of runners tested within 20 minutes of completing a marathon had

some level of pulmonary edema.

Dr. Yves St. James Aquino

Arecent study found that marathon

running can trigger pulmonary

edema, which may be associated with

physical signs of breathlessness, severe cough

and heart aack or respiratory failure in se-

vere cases.

Marathon running is worldwide. Half-

a-million people ran the marathon in the

United States this past year and in 2010. And

therefore, this is a big topic, said lead author

Dr. Gerald Zavorsky.

Researchers from the US and Italy aimed

to determine if pulmonary edema devel-

ops from long-distance running, character-

izing its incidence and severity. In addition,

researchers wanted to determine if the

resulting edema is related to nishing time.

The study involved 26 runners who par-

ticipated in the 2011 Steamtown Marathon

held in Scranton, Pennsylvannia, US. The

marathon started at an elevation of 452 meters

above sea level, with a net drop to 291 meters

at the nish line. The study noted that all run-ners nished with times between 142 and 289

minutes.

To quantify the presence of edema, pos-

teroanterior and lateral chest radiographs

of the runners were taken the day before the

race, then 19, 56 and 98 minutes aer nish-

ing the race. Three radiologists were tasked to

do the radiograph interpretation. The readers

worked independently and were not in con-tact with each other. They were also not told

which radiographs were taken before or aer

the race.

Four radiographic characteristics were

assessed, including peri-bronchial cung,

loss of denition of vascular markings, pul-

monary opacication and blurring of hilar sil-houee. The quantication of edema ranged

from 0 or no edema to 8 or severe edema. The

scores from each reader were then averaged.

Results showed that 50 percent of run-

ners had some level of pulmonary edema 20

minutes aer the race, and 20 percent of

those runners develop moderate to severe

pulmonary edema. In four runners (15 per-

cent), mild to moderate pulmonary edema

was even retained 1 hour aer nishing the


25/49


marathon.

Upon further evaluation, the study found

that women were at 13 times higher risk com-

pared with men in the development of pulmo-

nary edema (odds ratio 12.8, r2 0.31, P=0.038).No correlation was established between mara-

thon time and the development of pulmonary

edema, which suggests the risk of edema may

be prevalent across all abilities.

However, none of these athletes with radio-

logic nding of pulmonary edema exhibited

signs such as diculty of breathing or cough-

ing of blood.

According to Zavorsky, potential causes

may include stress failure of pulmonary

capillaries, uid-electrolyte imbalances, and

increased permeability pulmonary edema.

However, the most likely cause is increasedpulmonary wedge pressure, whereby pres-

sure within pulmonary artery force out uid

into the interstitium.

While pulmonary edema can be a negative

consequence of marathon running, regular exer-

cise can also keep you t and healthy. We do not

yet know the impact of this nding on long-term

health of runners, concluded Zavorsky.

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26/49


Flight hypoxia assessment inappropriate

for pediatrics

Dr. Yves St. James Aquino

British Thoracic Society (BTS)

recommendations on hypoxic ight

assessment are not appropriate for

pediatric patients, according to a study by

UK researchers.

The study involved 107 children age 0.1 to

19.2 years who were referred for a variety ofconditions including muscular dystrophy,

cystic fibrosis, severe asthma, long-term

ventilation, long-term oxygen therapy and

sleep breathing disorders.

The BTS recommendations aim to

enhance safety for passengers with lung

problems who are travelling by air, reduc-

ing the number of in-flight emergencies due

to respiratory disease. The BTS establishedupper and lower thresholds for no in-

flight oxygen required at percutaneous

oxygen saturation (SpO2) >95 percent or

in-flight oxygen needed at SpO2


27/49


Personal Perspectives

One of the major activities of the European Respiratory Society is

this annual congress and its been steadily growing, growing not

only in numbers, its been growing in importance, its growing in

global perspective For lung diseases, there is a huge disparity

in health care models, huge disparity in how to care for certain

patients. Infectious diseases, HIV/AIDS, lung cancer, COPD are

diseases that you know occur everywhere.

Dr. Klaus Rabe, President, European Respiratory Society,

Professor, University of Kiel, Germany

Its been an adventure. Its good because we could just go anywherewe want to go. For the lectures it is subdivided into four topics.

If you do not want the next topic, you go to the next hall. We try to

nd topics that are relevant to our subspecialty. We just aended

a pulmonary rehab session, because of the updates and we plan to

set up our own program.

Dr. Ma. Bernardita Chua, Consultant,

Perpetual Succour Hospital of Cebu, Philippines

Its already my fourth ERS, and Im a PhD fellow. The topics of

my PhD which I can also follow here are physical activities and

comorbidities in COPD patients. There are a lot of sessions I

have checked in my personal agenda. They were very good; the

symposia especially are very nice.

Hans van Remoortel, PhD Fellow, University Hospital

Gasthuisberg, The Netherlands

The topics I aended were not too bad. It depends on the subject.

Yesterday, I aended four sessions which were very interesting.

The topics Im interested in are COPD, pulmonary hypertension,

interstitial lung disease and infections.

Dr. Masoongo Masoongo, Consultant,

Arras Hospital, France


28/49


First global standards on assessing lung

function


Rajesh Kumar

The rst global standards on assessing

lung function in dierent age groups

and ethnicities, established through

international collaboration, promise to

revolutionize the way physicians diagnose

and manage lung disease.

Spirometry is the standard test for

measuring lung function. In the absence of a

global benchmark for interpreting its results,

someone described as abnormal in one clinic

can be labeled as normal in another. Also, an

adolescent can see his/her level of lung func-

tion decrease dramatically when the care is

transferred from pediatric to adult clinic. Sim-

ilar errors can occur if the individual patients

ethnicity and associated dierence in body

composition or stature are not taken into ac-

count.

Multinational researchers part of the

Global Lung function Initiative (GLI) 2012,

set up by the European Respiratory Soci-

ety to establish a consensus on the topic,

assessed data from 74,187 healthy non-smokers aged 3 to 95 years to derive

reference spirometric prediction equations

for Caucasians (N=57,395), African Americans

(N=3,545), and North (N=4,992) and South-

east Asians (N=8,255), including appropriate

age-dependent lower limits of normal. [ERJ

2012: DOI: 10.1183/09031936.00080312]

Forced expiratory volume in 1 second

(FEV1) and forced vital capacity (FVC)

between ethnic groups diered proportion-

ally from that in Caucasians. For individuals

not represented by the above four groups, or

of mixed ethnicity, a composite equation tak-

en as the average of the above equations was

established.

The rst standard lung growth chart

developed as a result of these equations will

help beer identication of children most

likely to benet from treatment, thereby

avoiding unnecessary medication for those

who dont need it, said Dr. Janet Stokes of

the Great Ormond St Hospital in London, UK,

while describing the clinical implications.

The chart will also improve diagnosis and

management of chronic obstructive pulmo-

nary disease, thus enhancing independence

and quality of life in the elderly, said Stokes.

The GLI-2012 lung growth chart will also

allow patients to understand the health of

their lungs and more eectively manage their

condition, or take steps to prevent develop-

ment or progression of lung disease, added

Ms. Monica Fletcher, chair of the EuropeanLung Foundation in Sheeld, UK.

Subsequent additional data from the

Indian subcontinent, Arab, Polynesian, Latin

American countries, and Africa will further

improve the equations in the future. How-

ever, their widespread use will depend on

timely implementation by manufacturers of

spirometry devices, said the researchers.


29/49


Home factors impact on kids asthma

medication complianceElvira Manzano

Family lifestyle and issues at home may

negatively aect childrens adherence to

asthma medication.

In a study of 93 children with asthma

conducted in the Netherlands, 72 percent

used >80 percent of prescribed doses forasthma. However, almost 30 percent had

poor adherence rates. Barriers to adherence

include parental and nancial problems,

as well as having busy parents. Another

common and striking nding was that

children (8 to 12 years) were given full

responsibility to take their medication with-

out parental support or supervision, resulting

in poor adherence. [ERJ2012. E-pub ahead ofprint]

The ndings emphasized how crucial

it is for health care professionals treating

children with asthma to carefully assess these

potential barriers so that appropriate

interventions can be put in place to correct

the problems, said lead study author Dr. Paul

Brand, from the University Medical Centre,

Groningen, Netherlands.Good adherence is achievable. In fact,

median adherence rate in the study was 93

percent at rst month and 90 percent at third

month. But when we conducted in-depth

interviews on 20 parents, 12 with low

adherence and 8 with high adherence, as

to what might be preventing their children

from following their treatment plan, they

presented several lifestyle factors, Brand

said.

Some parents, the delegators and

strugglers, did not succeed in geing their

children to take their medication prop-

erly. They said a range of things going on

in their lives prevented their children from

adhering to the treatment plan. Their

responses included: when he was 8, we feltthat he got to take [the medication] himself.

One parent even said: Forcing never works

it becomes a struggle, and we never do that.

Their answers were compared using an

electronic monitoring system. Although

parents in the low adherent group expressed

intentions to strictly follow the treatment plan

at the outset, they failed to do so during the

course of the study, Brand said. Struggling

families therefore require tailored support.

Some parents do not succeed in geing their kids with asthma to take

their meds.



30/49


He said comprehensive asthma care may

prevent intentional non-adherence, and

addressing parental illness and medication

beliefs is important. Excessive responsibility

for medicines to school-aged children drivesnon-adherence, he concluded.

The results were supported by Mr.

David Supple, a parent of an asthmatic child.

Speaking about his own experience, he said:

Inhaled glutathione may help cystic

fibrosis patients

Radha Chitale

Apreliminary trial on inhaled

glutathione (GSH) showed that it can

improve lung capacity in cystic

brosis (CF) patients with moderate tosevere airways obstruction.

CF is a chronic genetic disease that causes

mucus to build up in the lungs, diges-

tive tract, and other areas of the body, and

aects about 70,000 people worldwide,

many of them children.

Glutathione is an antioxidant therapy

used as a rst-line defense for the lungs

against oxidative stress.Lead researcher Dr. Cecilia Calabrese of

Second University of Naples in Italy report-

ed that three previous studies on inhaled

GSH in CF patients have shown promising

outcomes in terms of forced expiratory vol-

ume in 1 second (FEV1) and peak expiratory

ow, but these were performed on a limited

number of patients and only one study was

placebo-controlled.In the current trial, 94 CF patients from

Italy over age 6 were divided into a pedi-

atric group (6-18 years) and an adult group

(>18 years) and randomized to inhaled GSH

(10 mg/kg) or placebo.

Patients were excluded from the trial

if they demonstrated a decrease in FEV1

greater than 15 percent during a GSHinhalation test, where FEV1 is evaluated

before inhalation and 10 and 60 minutes

aer inhalation.

FEV1 was evaluated with spirometry

at months 1, 3, 6, 9 and 12. Patients were

questioned about their lifestyle, frequency

of exacerbations, hospital admissions and

antibiotic use at months 1, 6 and 12.

Preliminary results showed that inhaled

GSH is well tolerated by both pediatric and

adult CF patients.

Pediatric patients on GSH therapy did not

demonstrate signicant increases in FEV1 at

3 and 6 months aer beginning therapy com-

pared with the placebo group. Mean FEV1

levels at months 0, 1, 3 and 6 were 95.6

22.6 percent, 96.3 23.1 percent, 96.4 19.5

percent and 97.1 20.8 percent in the GSH

group, respectively, and 101.1 17.8 percent,

98.3 15.3 percent, 100.4 18.7 percent and

It can be chaotic having four children and

when we have given our son, Alex, respon-

sibility over his medication to control his

asthma, we have found his adherence slip

away. We are conscious of this now andwould encourage other parents to keep a

close eye on their childs level of adherence,

and to spot potential barriers before they

become a problem.


31/49

31 October 2012 Conference Coverage98.6 19.3 percent in the placebo group, re-

spectively.

Adults did show moderate increases

in FEV1 with GSH therapy compared with

placebo but this trend did not reachsignicance aer 6 months. Mean FEV1

levels at months 0, 1, 3, and 6 were 63.3

15.3 percent, 68.1 17.4 percent, 67.3 16

percent and 67.0 16.5 percent in the GSH

group, respectively, and 66.7 21.3 percent,

66.5 18 percent, 64.5 18.9 percent and

64.0 20.2 percent in the placebo group,

respectively.

However, pooled data on all patients

with FEV1 80 percent showed that signi-

cant improvement persisted 6 months aer

beginning therapy. Mean FEV1 increased to62.6 15/1 percent at 6 months from 58.3

13.2 percent at baseline (P=0.04).

Preliminary results seem to show that

inhaled GSH therapy is able to induce a

signicant increase of FEV1 in CF patients

aected by moderate to severe airway

obstruction, Calabrese said.

Smart Rx. Every Time.

www.MIMS.com


32/49

Rescue-ree days*

over 1 year3,4

Symptom-ree days**

over 1 year 3,4

88%

74%

Why Seretide gives

real patient benetsrom day one and over the

years to come1,2

DrugReliable

Partnership5

DosageTherightstrength

fortherightpatient5

DataSetting

standards5-7

Device

Familiarand

easy-to-use

5

Your patients can benet rom awell-known anti-infammatory andbronchodilator action or at least 12hours, with an established saety record Dose choice in asthma gives

you the ability to step up anddown i required

You can oer your patientsconsistent dose delivery 4 in aneasy-to-use device, with the addedoption o an aerosol i required5

An extensive body o evidence youcan rely on. Ecacy that has set thebenchmark in asthma management

* ost-hoc an llnalylll sisii o L.AL.. ee iaii n esr cu -u - ere daya ovev r weeks - ,, stratum :

Seree itideiiiii 8 vsvs FP 72% (2 (p< .


33/49

33 October 2012 Depression

Depression, other mental disorders

increase risk of early death

Radha Chitale

Mental disorders such as depression,

bipolar disorder and schizophrenia,

which may not require hospitaliza-

tion due to severity, can still increase risk of

premature death, according to a long-term

study of Swedish.

Mental disorders have been associated

with increased mortality, but the evidence is

primarily based on hospital admissions for

psychoses, said the researchers, who com-

piled data from psychiatric interviews with

Swedish men of mean age 18.3 years who were

conscripted for military service over a mean

22.6 years of follow up through national reg-

istries.

When diagnosed at conscription, depres-

sion was associated with double the risk of

premature death (age-adjusted hazard ratio of

1.81) and the presence of bipolar disorder in-

creased the risk of death by more than 5 times

(age-adjusted hazard ratio of 5.55). [Arch Gen

Psychiatry 2012;69:823-831]

In total, 1.09 million men were conscripted

between 1969 and 1994 of which 5.6 percentwere diagnosed at conscription with a mental

disorder.

Compared with men without mental ill-

nesses, men who were diagnosed later upon

admission to a hospital had mortality hazard

ratios of 5.46 for neurotic and adjustment dis-

orders and 11.2 for substance abuse disorders

not including alcohol.

Men admied to hospital for psychiatric rea-sons following conscription numbered 60,333,

10,665 of whom were already diagnosed dur-

ing conscription.

The mortality risk associated with other di-

agnoses aer adjusting for age, socioeconomic

status, blood pressure, body mass index, intel-

ligence, and education included hazard ratios

of 1.53 for depression, 5.19 for bipolar disorder,

2.52 for schizophrenia, 1.88 for personality dis-

orders, 1.62 for other non aective psychoses,

1.48 for neurotic and adjustment disorders,

2.38 for alcohol-related disease and 2.68 for

other substance abuse.

The associations were partially aenuated

by adjusting for smoking, alcohol intake, intel-

ligence, education and late-life socioeconomic

status but were not aected by early-life so-

cioeconomic status, body mass index or blood

pressure.

During the follow up period, 15,110 men died.

Age stratication of the 4,879 men who were

diagnosed during hospitalization who died

subsequently showed that mortality risk was

ve to 11 times higher for men born between

1951 and 1958 and seven to 29 times higher for

men born between 1968 and 1976.

The mortality risk remained signicantlyelevated even aer excluding about 20-32 per-

cent of deaths considered suicide.

This might be due to more severe disease,

particularly in the group diagnosed early, the

researchers noted.

The results of the all-male study population

were further limited by potentially unmea-

sured factors such as comorbid illness, lifestyle,

medications and varying access to healthcare,the researchers said.


34/49


Heart attack increases spouse depression,

anxiety

Elvira Manzano

The death of a spouse from heart aackincreases the risk of depression and anx-iety in the surviving partner, requiring an

increased use of psychotropic medications,

a large Danish study has found.

Losing a spouse or having a spouse ex-

periencing a non-fatal MI is a major publichealth issue for which there is very lile

awareness among physicians and policy

makers, said study author Dr. Emil Fosbl,

a cardiologist and researcher at Denmarks

Gentoe University Hospital, Hellerup,

Denmark. People involved with patient

care should be aware of spouses mental re-

actions aer a life-threatening event such as

an MI. I would like to see a more formal wayof screening spouses for depression in rela-

tion to the event, but also subsequently.

Using data from Danish national regis-

tries, Fosbl and colleagues compared the

incidence of hospital system contact (hos-

pital admission or ambulatory visit), use of

antidepressants and benzodiazepines, and

suicide among spouses of patients who had

fatal and non-fatal MI (16,506 and 44,566,respectively) for the rst time with those

whose spouses died or were hospitalized

for other causes (49,518 and 131,564, respec-

tively).

The study found the incidence of depres-

sion was signicantly higher among spouses

of patients who had myocardial infarction

(MI), fatal or nonfatal, compared with those

whose spouses had non-MI events (pre-post,

P


35/49


Rajesh Kumar

The antidepressants uoxetine and venla-faxine are ecacious as short-term ther-apy for major depressive disorders in all age

groups, according to a large meta-analysis.

The researchers pooled data from more

than 9,100 patients of all ages with major

depressive disorder who had been included

in a total of 41 randomized clinical trials of

uoxetine (N=20 trials) and venlafaxine (N=21

trials). They carried out a reanalysis of all

person-level longitudinal data for the rst 6

weeks of active treatment. [Arch Gen Psychia-

try 2012;69:572-579]

They found that patients in all age groups

had signicantly greater improvement com-

pared with those receiving placebo, although

the dierential rate of improvement was larg-

est for adults receiving uoxetine (34.6 per-

cent greater than those receiving placebo).

Youth had the largest dierence in response

rates (24.1 percent in treated vs. control) and

remission rates (30.1 percent), with adult dif-

ferences generally in the 15.6 percent (remis-

sion) to 21.4 percent (response) range.Geriatric patients had the smallest drug-

placebo dierences, an 18.5 percent greater

rate of improvement, 9.9 percent for response

and 6.5 percent for remission. Also, immedi-

ate-release venlafaxine produced larger ef-

fects than extended-release venlafaxine, and

baseline severity did not aect symptoms.

This is the rst research synthesis in this

area to use complete longitudinal person-

level data from a large set of published and

unpublished studies.

Most studies included in the meta-analysis

were designed for achieving regulatory ap-

proval and do not demonstrate the maximum

eect a drug can produce. Some studies were

as short as 6 weeks whereas the maximum ef-

fect during an acute treatment episode is like-

ly 12 weeks or longer, the researchers argued.

The [current] study highlights many of

the limitations of meta-analysis that combine

evidence from multiple RCTs, concluded theresearchers.

It further highlights advantages of more

complete personal-level analysis when such

data are available and increases the need for

caution regarding interpretation of meta-an-

alytic results when person-level data are not

available.

Short-term fluoxetine, venlafaxine

efficacious for depression


36/49

36 October 2012 News

Saras Ramiya

Selected proton pump inhibitors (PPIs)

are safe for long-term use in patients

with chronic gastrointestinal (GI) con-

ditions, a study shows.

The new landmark international study

looked at the long-term eects of pantopra-

zole in patients with chronic GI conditions

such

medical tribune october 2012 sg

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