medical tribune july 2012 ph

7/31/2019 Medical Tribune July 2012 PH

1/48

www.medicaltribune.com

July 2012

OSA can be successfully managed in

primary care

CONFERENCE

Promising drug

combination forbreast cancer

IN PRACTICE

NEWS

Chengdu

Land of Tea,Tao and Pandas

FORUM

Therapeutics in

osteoporosis

Surviving the

approaching tsunamiof diabetes


2/48

2 July 2012

Rajesh Kumar

Patients with obstructive sleep apnea (OSA)can be successfully managed in primarycare by suitably trained GPs and nurses, ac-

cording to Australian researchers.

Previous studies have shown that ambula-

tory models of care for OSA in specialist clin-

ics can produce patient outcomes comparable

to laboratory-based management. However,

this is the rst randomized controlled study

to be conducted in primary care.

Researchers randomized 155 patients with

OSA to either primary care-based manage-

ment or usual care in a specialist sleep center.

At 6 months, mean change in Epworth sleepi-

ness scale (ESS) scores, the primary outcome

measure of the study, was similar in the two

groups (4.9 in the primary care group vs. 5.1

in the specialist group).

GPs identied patients with symptomatic,

moderate-to-severe OSA using a four-item

screening tool, the ESS, and home oximetry.

Primary care-based management was led

by the patients GP and a community-based

nurse and involved use of home auto-titrat-ing of continuous positive airway pressure

(CPAP). Usual care in a specialist sleep center

involved management by a sleep physician

and laboratory-based testing.

In addition to similar changes in ESS scores

at 6 months, mean change in Functional Out-

comes of Sleep Questionnaire (FOSQ) score

was similar in the two groups (2.3 in the prima-

ry care group vs. 2.7 in the specialist group), aswas compliance with CPAP. Mean daily use of

CPAP was 4.8 hours in the primary care group

and 5.4 hours in the specialist group.

Within-study costs for primary care man-

agement were lower than those for specialist

care, with signicant savings of A$2,157 (95%

CI: A$1,293 to A$3,114) per patient.

With the rise in demand and growing

waiting lists for sleep physician consultation

and laboratory-based sleep services, there hasbeen increasing interest in development of

ambulatory strategies for the diagnosis and

management of OSA involving home sleep

monitoring and auto-titrating CPAP, said

lead author Dr. Ching Li Chai-Coetzer of the

Adelaide Institute for Sleep Health at Repatri-

ation General Hospital, Adelaide, Australia.

The results showed that a simplied ap-

proach for the treatment of OSA in primarycare was not clinically inferior to manage-

OSA can be successfully managed in primary

care

A randomized study involving 155 patients with OSA has shown that a

primary care-based management approach can produce outcomes compa-

rable to usual specialist care.


3/48

3 July 2012ment of these patients in a specialist sleep

center. These were recently presented at the

American Thoracic Society international con-

ference 2012 in San Francisco, California, US.

This approach also oers a lower cost al-ternative to usual care. In addition, waiting

lists for specialist sleep centers are long, and

home care may be preferred by patients, said

Chai-Coetzer.

Rather than a move to transfer the man-

agement of OSA from specialist to primary

care, he envisioned GP model of care to be

complimentary to specialist care, with GPs

working alongside specialists to help relievethe excess burden of untreated disease in the

community and to expedite treatment.

This would be particularly benecial for

rural and remote regions, as well as develop-

ing nations, where access to specialist services

may be limited, he said, adding that histori-

cally, chronic conditions like asthma and dia-

betes were treated only by specialists, but are

now commonly managed in primary care.

Dr. Ong Thun How, director of the sleep

disorders unit at Singapore General Hos-

pital, agreed a greater role for GPs could befeasible, but said the awareness of OSA among

them is still not very good due to insucient

exposure to various aspects of sleep medicine

at undergraduate and postgraduate level.

In an aempt to ll some gap, Ongs unit is

organizing a sleep symposium on 13-14 Oc-

tober this year focusing on management and

diagnosis of OSA and will also run a concur-

rent CPAP workshop that will help GPs learnhow to manage patients on CPAP.

The study ndings may not be applicable

to all as the participants were relatively well,

community-screened patients. Those with

more complicated disease, eg, respiratory fail-

ure and/or concomitant heart disease, will still

probably need specialist care, Ong added.


4/48

4 July 2012 Forum

Surviving the approaching tsunami of

diabetes

Excerpt from a speech by Ms. Geralyn R Spolle, American Diabetes Association (ADA) president of

health care and education, during the ADAs 72nd scientic sessions held recently in Philadelphia, Penn-

sylvania, US.

One person is diagnosed with diabetes ev-ery 17 seconds. This one person could beyour family member, your child, or the man

that rides next to you on the train to workeach morning.

For many of us, diabetes has been our lives

work. Unfortunately, there is enough work

in this eld to last for generations to come.

My fondest dream is to hold high the vial of

a miraculous serum as Jonas Salk did when

he announced the polio vaccine, and tell you

that I and my colleagues have found a cure

for diabetes and our mission is fullled: a lifefree of diabetes and all its burdens!

However, lately I have been having two

recurring nightmares. In one, there are lines

and lines of people, all with diabetes, who

are typing their name into a vast computer

program. They ll out a questionnaire and

then download a list of lab work to be done

prior to their 3-minute telephone or online

appointment time.The lucky ones will talk with a real per-

son. The unlucky ones will get an automated

response from a very clever program that al-

lows them to select options, similar to the one

employed by airlines. But instead of a voice

asking you if you want ight information, it

will ask you to click 1 if you need insulin or

dietary adjustments.

My second nightmare, unfortunately, is

real. It is the story of a village in the Middle

East where persons with diabetes can buy

only one vial of insulin. Each person gets

their share of 20 units; just enough to keep

them alive and functioning.

When I hear that 380 million people in

the world are expected to have diabetes by

2025, I dont see a number. I see people like

my patients and these villagers who struggleeveryday to live a life with a disease that de-

mands so much and gives back so lile.

We are currently in the midst of a tsuna-

mi of diabetes. Its rst wave is the ever ris-

ing wave of obesity, the underlying current

of the increase in diabetes. Worldwide, 2.8

million people die as a result of being over-

weight or obese and the prevalence of obesity

has doubled between 1980 and 2008. North

America leads the trend with more than 30

Around 380 million people globally are expected to have diabetes by

2025.


5/48

5 July 2012 Forum

percent people being obese, closely followed

by the tip of Africa and the Middle East. Asia

and Europe are close behind, with a preva-

lence of between 20 to 29 percent obesity.

The second wave is hyperglycemia.Worldwide, the alarming rise in the inci-

dence of hyperglycemia closely follows the

obesity trend and these show no signs of

abatement. According to the International

Diabetes Federation, there were 284.6 mil-

lion people with diabetes worldwide in 2010,

which is expected to grow to 438.4 million

by 2030. The greatest increases will occur in

Africa and the Middle East. In North Africa,

greater than 90 percent increase is expected,

followed by South East Asia and South and

Central America.

Not only is diabetes a healthcare crisis,

it is also an economic one since it will send

destructive shockwaves through economies.

Diabetes aects the most productive age

group of 40 to 59, which in turn aects gross

national productivity.

We must take the necessary steps to sur-

vive this tsunami by rst sounding the alarm

to warn the public of the dangers to come,

preparing ourselves and the healthcare sys-

tem to reduce the impact and, ultimately,

taking to the higher ground.

There is false information, misconceptions

and myths about diabetes in every sector ofour society, including amongst healthcare

professionals. Diabetes is a disease without

a face. Theres lile recognition of its poten-

tially life threatening nature or the demands

of daily care. For the public, it is: Dont eat

your sugar and take those (insulin) shots ev-

ery day. But it is much more than just that.

We must convince the public that diabe-

tes is a serious disease, with serious personaland societal consequences. Next step is for

clinicians and educators to help reduce the

impact of diabetes by supporting research

into prevention, cure and care of those al-

ready aected, and by increasing the re-

sources devoted to research.Research shows that despite comparable

diabetes care, some groups have poorer

health outcomes than others. Factors such

as physician interaction, prevalence of undi-

agnosed or untreated depression, fewer re-

sources, greater stress associated with socio-

economically deprived neighborhoods and

out of pocket costs are important for deter-

mining outcomes.

Improved healthcare delivery systems

must, therefore, focus on making it more

cost eective and easier to deliver diabetes

care within primary care seings, with eas-

ier access to self care plans. Ongoing sup-

port for self-care in the form of newsleers,

email, social media, community board post-

ings, access to information lines and diabe-

tes educators is absolutely necessary. Cur-

rently, access to these programs is limited in

the government and private sectors.

The next step is to take to the higher

ground, ie, making change happen. That is

the ethical and the right thing to do. If every

single one of us was able to inform the public

and heighten the awareness of the dangers

of a growing diabetes epidemic, just thinkwhat we could accomplish. We are all stake-

holders in our healthcare system: whether

researcher, educator or clinician.

The current healthcare systems respond

best to acute and episodic care. But that mod-

el will not address the burgeoning needs of

a population requiring chronic care. Change

must start here and now, with those of us

who are touched by diabetes and have madeit our lives work.


6/48


7/48

7 July 2012 Philippine Focus

New tax measure to ensure better health

for Filipinos

Gabriel Angelo Sembrano, RN

O n June 6, 2012, HB 5727 as amended,otherwise known as the Sin Tax Reformbill, was approved in a remarkable move by

the Lower House. Certied as an urgent bill

by President Benigno Simeon Aquino III, the

passage of the law is now in the hands of thesenators. The current sin taxes have already

been frozen for 16 years due to the price

classication freeze, which preserved low tax

rates for all brands existing since 1996.

According to Dr. Anthony Leachon, non-

communicable diseases consultant of the De-

partment of Health (DoH), HB 5272 as amend-

ed aims to reduce consumption of these sin

products. Health is the primary objective aswe are not only talking about the health of one

segment or market, but the health of a nation.

He adds that the current tax rates have

proven to be ineective in curbing cigaree

and alcohol consumption as it is shown that

consumption is continuously on the rise.

The signicant tax increase is an aempt to

catch up on the large health and economic costs,

which, according to a study of Dr. Antonio Dansof the Philippine General Hospital, amounts to a

minimum of P188 billion in 2011. This is due to

tobacco-related deaths and diseases that low tax

rates have caused the Philippines.

Leachon mentioned that if the bill pass-

es, funds generated will ultimately trickle

down to the farmers and the general popu-

lace through the Universal Healthcare Pro-

gram (UHC). Farmers will be assured of a

safety net through programs that support

alternative livelihoods. The Filipino people,

especially the poor, will benet from beer

health facilities, enrollment in PhilHealth

and other health-related gains.

Our sin tax for tobacco is the lowest in

Asia. The cost of cigarees in the Philippines

is the lowest in the region accounting for the

prevalence rate of smokers among the youngand the poor, Leachon pointed out. In eect,

around 28.3% of the adult population smoke

and an alarming 48% of teenagers engage in

such practice.

Currently on the average, 240 Filipinos

die daily because of smoking-related diseas-

es, Leachon added. This translates to 180 to

300 billion pesos a year in expenditures.

Leachon noted that HB727 as amendedis essentially progressive since there will be

transfer of funds, which is around 33 billion

pesos, from the sin tax to the sick, young

and poor through the earmarking of funds

for the UHC program. This will cushion the

poor from the economic and health burdens

brought about by consumption of sin prod-

ucts.

The Philippines is a party to the FrameworkConvention on Tobacco Control (FCTC), the rst

international health treaty where we pledged to

reduce smoking prevalence from 28.3% at pres-

ent to 25% by 2014, according to Leachon.

We need to inform and inuence decision

makers particularly the senators who will be

reviewing and approving the sin tax bill. A

collaborative and multi-sectoral approach is in

order to push the bill to its fruition, Leachon

said.


8/48


High prevalence of coronary arterydisease seen in adults with CHD

42nd Philippine College o Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

Dr. James Salisi

A

study by Dr. Melgar Matulac et al., re-

vealed high prevalence of coronary ar-

tery disease (CAD) among adult patients with

congenital heart disease (CHD) in a review of

patients who underwent coronary angiogram

at the University of the Philippines-Philippine

General Hospital from 1998 to November

2012. Spurred by the scanty data on the preva-

lence of CAD in adults with CHD, the inves-

tigators found a higher prevalence of CAD

at 11.5% than the general population. This is

an important nding since coronary angiog-

raphy is not routinely done in adult patients

with CHD and could potentially alter survival

outcome by mitigating complications of CAD

through early detection and treatment.

The study aimed to dene the risk for myo-

cardial ischemia as the risk of acquiring coro-

nary artery disease increases with age; the

survival outcomes of patients with congenitalheart disease reaching adulthood has steadily

improved. Past studies have only concentrat-

ed on hemodynamic aspects of the congenital

lesions resulting in scanty data on the burden

of CAD in adults with CHD.

In this study, 90 adults with CHD who un-

derwent hemodynamic assessment and in-

terventions at the UP-PGH Catheterization

laboratory from 1998 to 2011 were initially in-cluded. Fiy two underwent coronary angiog-

raphy and 52 percent of this cohort who were

40 years old and above underwent routine

diagnostic assessment to rule out presence of

coronary artery disease prior to planned in-

terventions.

Patients with all types of CHD were in-

cluded and classied as simple, intermediate

or complex CHD.

Signicant coronary artery disease was

found in 11.5 percent of patients who under-

went coronary angiography. All of them were

40 years old and above, four of them are fe-

male, ve of them had documented tradition-

al CVD risk factors like hypertension. None of

the patients with signicant CAD had cyano-

sis while four patients had typical chest pain.

Majority of CHDs were simple and com-

prised mostly of atrial septal defects (36%).

Four (70%) patients with simple CHD and

2 (30%) with intermediate CHD had signi-cant CAD, but patients with complex CHD

had none. Patients with complex CHD rarely

reach adulthood and this in part explains the

zero incidence of CAD in this population.

The prevalence of CAD in adults with

CHD is higher in this study than in the

general population without suspicion of

CAD of similar age. The absence of cya-

notic patients was suggested to be due to itsprotective eects against coronary atherosclerosis.

CONFERENCE COVERAGE


9/48


Systemic arterial hypertension was the

most common risk factor. Other risk factors

were dyslipidemia and diabetes. Smoking his-

tory is present in 1 in 5 of those with CAD. Pa-

tients with signicant CAD in this study hadat least one cardiovascular risk factor, which

highlights the need for primary prevention of

CAD in adults with CHD.

The ndings of this study support the rec-

ommendation of routine coronary angiography

among adult patients with CHD who are 35 years

old and above and with traditional cardiovascu-

lar risk factors. The study bolsters the case forprimary prevention of CAD and modication of

traditional CV risk factors applied to the general

population.

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10/48


Dr. Yves St. James Aquino

D iagnose early and dierentiate pulmonaryarterial hypertension (PAH) from pulmo-nary hypertension (PH) for beer management,recommended Dr. Darren Taichman, seniormedical associate under the Medical EducationDivision of the American College of Physicians.

According to consensus guidelines, pulmo-nary hypertension is hemodynamically de-ned as mean pulmonary arterial pressure of>25 mmHg, while pulmonary arterial hyper-tension is dened as pulmonary arterial pres-sure of >25 mmHg with normal pulmonarycapillary wedge pressure or le ventricularend-diastolic pressure of


11/48



P

rophylactic platelet transfusion for patientstreated for acute dengue infection did not

demonstrate signicant benets over other treat-ment modalities, according to a retrospectivecohort study conducted at the United DoctorsMedical Center (UDMC) by Dr. Edgel Nazarenoet al.

The main objective of the study is to elu-cidate that prophylactic platelet transfusion

brings considerable positive eects on pa-tients with acute dengue infection.

In obtaining the socio-demographic data,signs and symptoms present, treatment andclinical outcome data, the investigators re-viewed a total of 149 medical charts of pa-tients aging 19 years old and above who wereadmied at the UDMC from July 1, 2009 to

June 30, 2011, presenting with acute febriledisease lasting for 2 to 7 days and falling un-der the case denition for dengue hemorrhag-ic fever or dengue hemorrhagic syndrome bythe World Health Organization. Not includedwere patients who had other active infectionssuch as pneumonia, UTI, tonisillitis, typhoidfever, etc. Also excluded from the study werethose who had unstable co-morbidities likestroke, diabetes mellitus, hypertension, livercirrhosis and other liver diseases that can al-ter the course of the infection.

Patient records were then grouped into

three categories: patients who were observedwith strict monitoring of the level of hydra-

tion (group 1), patients given platelet trans-fusion as prophylaxis even without signs ofactive bleeding (group 2), and patients givenplatelet transfusion as therapeutic for pa-tients with signs of active bleeding (group3).

Based on the generated results in the study,hematocrit levels prior to platelet transfu-sions, group 2 presented with the highest level(0.45 versus 0.41 for groups 1 and 3; p=0.001).The white blood cell count and proportion ofsubjects with >0.50 hematocrit level were es-sentially the same among the three groups.The lowest level of platelet count reached was

signicantly greater in group 1 than in thetwo other groups, while groups 2 and 3 didnot show signicant dierence. At the time ofplatelet transfusion, dierence in the plateletcount between groups 2 and 3 were border-line signicantly dierent with a trend to-wards higher count in group 3 than in group2. In terms of the length of stay of patientsin the hospital, group 3 showed signicantly

longer stay when compared to group 1 butnot with group 2, while groups 1 and 2 didnot have any signicant dierence.

The researchers concluded that prophylac-tic platelet transfusion in cases of acute den-gue infection does not present added benetsfor patients over other treatment modalities.The World Health Organization stresses thatprompt and rapid resuscitation from shockand correction of metabolic and electrolyte

imbalances prevent disseminated intravascu-lar coagulation.

Preemptive platelet transfusion notneeded for acute dengue infection


CONFERENCE COVERAGE


12/48



Obstructive Sleep Apnea (OSA) is a po-

tentially life-threatening disorder, saidDr. Virginia de los Reyes of San Juan de Dios

Hospital. Usually marked by loud snoring,

patients with OSA have 2 to 7 times the risk

of guring in vehicular accidents due to loss

of alertness than those without such disorder.

In addition, there is also higher risk for com-

plications, like systemic hypertension, pul-

monary hypertension, myocardial infarction,

cerebrovascular diseases, cardiac arrhythmiasand metabolic syndrome.

In reality, the OSA patients do not actu-

ally visit clinics with complaints of snoring, or

apnea even. They usually come to our clinics

because they are already suering from car-

diovascular complications. So, it is the role of

the internists to try to dig deeper if they have

underlying OSA and be able to manage it

properly, de los Reyes said.According to de los Reyes, OSA is one of

the most common sleep disorders character-

ized by repetitive episodes of upper airway

obstruction that occur during sleep and is as-

sociated in the reduction of blood oxygen sat-

uration. This is usually caused by decrease

in muscle tone, increased so tissue around

the airway or structural features that give rise

to narrowed airways like enlarged tongue or

enlarged tonsils that eventually reduce the

cross-sectional area of the upper airway lu-

men.

In diagnosing OSA, de los Reyes stressed

that polysomnography (overnight sleep

study) is the gold standard diagnostic test.This test does not only conrm the diagnosis,

but it also determines the severity of the dis-

ease and the best management approach.

For treatment, de los Reyes advises pa-

tients to lose weight, especially those who are

obese.

We try to tell them to keep their weight

at a normal BMI, said de los Reyes. She also

recommends postural therapy where patients

with OSA sleep on their side, So there is a

Specialist warns against the dangers ofsleep apnea


CONFERENCE COVERAGE


13/48


small propensity for their tongue to fall back-

wards and block the airway.

De los Reyes pointed out that the gold stan-

dard for treatment of moderate to severe OSA

is continuous positive airway pressure (CE-PAP). In CEPAP, [the] machine blows air to

a tube and the tube is connected to a nasal or

facial mask. The air is transmied to the air-

way and it acts as a pneumatic splint opening

the obstructive airway. With this, the patient

is able to breathe properly, de los Reyes said.

The mortality risk increases for those OSA

patients without treatment but it becomes

similar to the general population when they

are compliant with CEPAP, said de los Reyes.

For mild OSA, other non-invasive treat-ment options are available, such as tongue

retaining device and mandibular position-

ing design. In some cases where the non-

invasive treatments fail, surgery could be

an option for correctable abnormalities like

enlarged tonsils.

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14/48


Dr. James Salisi

R esistant hypertension remains a chal-lenge and this is expected to becomemore so as the population is aging, said Dr.

Romeo Divinagracia from the Philippine HeartCenter. He emphasized the need to identify re-

sistant hypertension in patients for the quality

of life and survival benets that directed diag-

nostics and therapy may give them.

A persistently elevated blood pressure

above 140/90 mm Hg in spite of taking three

antihypertensive agents of dierent classes

including a diuretic denes resistant hyper-

tension. It is primarily a systolic problem andis related to age.

Dicult-to-treat hypertension is present in

30 percent of the geriatric population but only

5 percent have resistant hypertension, high-

lighting the need to dierentiate true resistant

hypertension from psuedoresistance.

We need to identify patients who are at

risk of having reversible causes of hyperten-

sion who may benet from special diagnos-tics and therapeutic considerations, Garcia

emphasized.

Recommended workup of patients with

resistant hypertension is a two-step process.

First, conrm that it is indeed resistant hy-

pertension by ruling out or correcting factors

associated with pseudoresistance. Second,

identify the true factors involved in treatment

resistance.

Citing Garj et al., on the causes of resistant,

Garcia pointed to drug-related causes in 58

percent, non-adherence to medications in 16

percent, and psychological causes in 9 percentof patients as the top three causes of resistant

hypertension.

Medication adherence is a common issue

among hypertensive patients. Compliance

with medication is dicult in many cases

and this is unfortunate since 80-percent com-

pliance is needed in order to have pharma-

cologic benet. Exogenous substances like

NSAIDS for arthritis and pains, symphatomi-metic drugs like phenylephrine and steroids,

and herbal preparation may raise the blood

pressure in patients taking antihypertensive

medications.

Pseudoresistance may be caused by mea-

surement artifact, white-coat hypertension,

pseudohypertension and physician inertia.

Improper BP measurement may give falsely

elevated BP while psuedohypertension in theelderly is brought about by heavily calcied

arteries that no amount of antihypertensive

medication could adequately treat.

Other diseases associated with resistant

hypertension may include renovascular dis-

eases, Cushings disease, tumors, genetic dis-

eases and obstructive sleep apnea. Lifestyle

causes include obesity, alcohol, drugs and

high-salt intake.

Resistant hypertension remains a challenge


CONFERENCE COVERAGE


15/48


Patients may benet from interventional

management like renal symphatetic denerve-

tion using radiofrequency ablation, surgical

sympathectomy, and baroreceptor modula-

tion. These modalities intervene at the ana-tomical level to reduce blood.

Radiofrequency is used to ablate nerve bers

at the renal arteries adventitial layer. Although

it is a dicult procedure to perform, it has been

shown that in a period of over a year aer de-

nervation, there is a sustained and progressive

reduction in both systolic and diastolic pressure.

Surgical symphatectomy has reduced blood

pressure in patients but may have intolerableside eects like urinary and sexual dysfunction.

Baroreceptor stimulation by Rheos device in-

serted via the carotid nerves allow for personal-

ization of treatment goals.

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16/48


Dr. Yves St. James Aquino

Ameta-analysis of controlled trials

showed dabigatran etexilate as an eec-

tive alternative to enoxaparin in prevention

of venous thromboembolism (VTE) aer or-

thopedic surgery, according to a study done

by Dr. Mary Shiela Ariola et al., of the Cardi-

nal Santos Medical Center.

Using Jadad criteria for evaluation, the

meta-analysis included randomized, con-

trolled trials published in PubMed and Med-

line involving an oral direct inhibitor, dabi-

gatran etexilate, as an experimental drug

that was compared with enoxaparin in the

primary prevention of VTE in patients un-

dergoing elective total hip and knee arthro-

plasty. Primary ecacy outcome is the ma-

jor VTE events and VTE-related mortality;

while the major safety outcome is the occur-

rence of major bleeding events during studytreatment.

Results showed that dabigatran 220 mg

OD had signicant benet in preventing

total VTE events and VTE-related mortal-

ity (RR-0.80; CI=0.60-1.06). Dabigatran 150

mg OD was proven to be less eective in

preventing total VTE events and mortal-

ity (RR=1.14; CI=0.83-1.57), but causes less

bleeding events.

Heterogeneity tests comparing both doses

of dabigatran against enoxaparin in prevent-

ing VTE events showed that all the studies

were homogenous. Similar results were seen

in testing for the heterogeneity of dabigatran

and enoxaparin in the occurrence of major

bleeding events. The study suggested that

dabigatran 220 mg OD is a safe, eective and

possibly a superior alternative to enoxaparin

for thromboprophylaxis in adults undergo-

ing major lower limb orthopedic surgery.

The study stated that according to the

American College of Chest Physicians, post-

operative VTE was the second most common

medical complication and the second most

common cause of excess length of stay. Useof thromboprophylaxis could provide ben-

et to patients, according to the study.

Results of the meta-analysis indicate that

oral dabigatran is a promising anticoagulant

and alternative to enoxaparin in preventing

major VTE events.

Dabigatran can be an alternative toenoxaparin for VTE, study says


CONFERENCE COVERAGE


17/48


Dr. Antonio Dans

President

Philippine Society of General Internal Medicine

T he practice of general internal medicine(IM) has been facing diculty with thetrend of en masse subspecialization, and it

was only logical for general internists to want

to protect its eld of practice.

It has not been a part of the mission and vi-

sion of the Philippine College of Physician to

advocate careers in general internal medicine.It is not in their explicit mission and vision

statement. And so, this has been a neglected

eld, said Dr. Antonio Dans, founding presi-

dent of the Philippine Society of General In-

ternal Medicine.

According to the societys website, in May

of last year, 172 internists and three past pres-

idents of the Philippine College of Physicians

signed a manifesto calling for the formation

of a new medical society. And on November

11, 2011, PSGIM was ocially founded.

In building an organization that advocates

internal medicine as a career, Dans could nothelp but emphasize the importance of prima-

ry care.

All advanced countries are moving to-

wards improving primary care. And to im-

prove primary care, you need a good pri-

mary-care workforce. And to get a good

primary-care workforce, you need people ad-

vocating careers in primary care, Dans said.

This is one of the main reasons why Danschose to practice general internal medicine in

the rst place.

I went back to general IM because I was not

happy with my career as a cardiologist. I felt

compelled to ignore a lot of my patients symp-

toms, because I felt someone else should be look-

ing at those symptoms. But what happened to

those patients many times, their health fell apart,

and I felt partly responsible, shared Dans.As a young organization, the society has

come up with a three-point goal to help im-

prove the practice, according to Dans.

First, we have to make sure that we listen

to and speak with our members. Thats com-

munication between the leadership and the

membership. Dans explained that they have

the advantage of social media on their side,

with a strong Facebook presence and a grow-

ing Web-page audience.

General internists resuscitate a challenging

field

The Medical Tribunes Dr. Yves Saint James Aquino talks to presidents o specialty societies to discuss

their roles in promoting their respective felds

NOTES ON LEADERSHIP


18/48


Second, to make sure to increase the sup-

ply of general internists and making sure its

not just quantity, but quality. We want a sup-

ply of high-quality internists, he claried.

And lastly, Dans wants for the society toalso work on the demand side. The society

recognizes the need to work with PhilHealth,

the Department of Health, and Universal

Healthcare to help them understand the need

for general internal medicine.

We have convinced the PCP to require

that all certied training programs around

the country have at least one general inter-

nist, reported Dans.

As the medical society turns to face thepublic, Dans could not have stressed it more,

saying, They need us. The country needs

us. But they dont know it yet. The country

doesnt know it yet.


19/48


Nutrient supplementation for healthier eyesand bones

As people age, physiological changes occurin the eye, including reduced peripheralvision and exibility of the eye, degeneration

of muscles of the eye and clouding of the lens.1

Age-related macular degeneration (AMD),

the primary cause of irreversible blindness or

severe vision impairment among the elderly,may also occur.2 Some of the risk factors for

AMD include age, race (Caucasians), family

history, co-morbidities like cardiovascular dis-

ease and hypertension, and smoking.

Antioxidant vitamins and certain minerals

have been found to decrease risk or progres-

sion of eye diseases. The Age-Related Eye Dis-

ease Study, which involved 4,757 elderly par-

ticipants aged 55 to 80, evaluated the naturalhistory and risk factors of AMD and cataract

and how high doses of antioxidants and zinc

may aect disease progression. Results from

the study showed that high levels of zinc and

antioxidants such as vitamin C, E and beta-

carotene signicantly reduced the risk of ad-

vanced AMD and its associated vision loss.3

These antioxidants and zinc are said to

be recommended for participants who haveat least intermediate risk of developing ad-

vanced AMD.3

Besides visual changes, the elderly may

also experience decline in bone mass, which

oen begins in the fourth decade. The linear

decline in bone mass is at a rate of about 10%

per decade for women and 5% per decade for

men.4

Muscles, joints and bones go through phys-

iologic changes as we age, and these changes

ADVERTORIAL

may lead to arthritis, postural changes, and

even spontaneous fractures.5

Two nutrients essential for bone health

are calcium and vitamin D, a vitamin that

promotes intestinal calcium absorption and

bone matrix mineralization. Studies have

shown that reduced supplies of calcium areassociated with decreased bone mass and

osteoporosis, and a chronic or severe de-

ciency in the vitamin leads to osteomalacia,

which presents with defective bone min-

eralization.6 Due to risk of skin cancer and

other skin diseases, sun exposure as a main

source for vitamin D is considered limited,

and supplementation may be necessary to

prevent vitamin D deciency.6Calcium supplementation has been found

to reduce the rate of bone loss in osteopo-

rotic patients, with more recent studies

demonstrating a benet not only on bone

mass maintenance but also on reduction in

fracture incidence. The best way to achieve

adequate calcium intake is through the diet,

but when dietary sources are scarce, supple-

mentation may be necessary.6

References:

1. Smith S and Gove J. Physical Changes o Aging. University o Florida, IFAS

Extension, 2010.

2. Woo JH. Singapore Med J, 2008;49(11):850.

3. Chew E. Use o Antioxidants, Vitamins, and Minerals in Age-Related Eye

Diseases. NIH Publication accessed rom http://ods.od.nih.gov/pubs/

elderly.14jan03.abst.chew.pd last June 14, 2012.

4. Boss G and Seegmiller J. The Western Journal o Medicine, 1981;6(135):434-441.

5. Lata H. Ageing: physiological aspects. JK Science, 2007(9)3:11.6. Gennari C. Calcium and vitamin D nutrition and bone disease o the elderly.

Health Nutr. 2001 Apr;4(2B):547-59.


20/48


A surgeons pioneering work in medical

informatics

BEYOND THE CLINIC

Dr. James Salisi

I n the Philippines, the name of Dr. AlvinMarcelo is synonymous to medical infor-matics, a eld where he has done pioneering

work by bringing the power of informationcommunication technology to the practice of

medicine.

Marcelos interest in computers started ear-

ly on in high school at the Ateneo de Manila

where he was part of the rst batch to have

computer programming classes.

He described ending up in medical infor-

matics as a full big round circle for him.

I placed computer science as my secondchoice in UPCAT. Biology as rst choice (pre-

med) and then checked the box for Intarmed,

he said. He went into surgical training at the

University of the Philippines-Philippine Gen-

eral Hospital (UP-PGH) aer graduating from

the UP College of Medicine.

While surgery is not exactly the eld that

one would immediately associate with com-

puters, Marcelo found that his passion forcomputing and the skills that he acquired in

high school would become handy as he be-

came the de facto computer troubleshooter

among the residents of the Department of

Surgery at UP-PGH.

When I ended up in surgery (and surgery

was one of the departments that could aord

computers per division), I pulled out my high

school skillsand my passion for computing

was rekindled, he wrote through email.

Another UP Medicine graduate who at-

tended a course on Medical Informatics at

Stanford University, Dr. Cito Maramba, in-troduced Marcelo to the eld that brings ICT

and medicine together.

Aer his training at UP-PGH and as a con-

sultant of the Department of Surgery, Marcelo

le the country for a two-year postdoctoral

fellowship in medical informatics at the US

National Library of Medicine in Bethesda,

Maryland. His areas of research interests were

in telepathology, mobile computing, and bib-

liometric analysis of MEDLINE content.


21/48


Upon coming back, he established the

Master of Science in Health Informatics at the

UP Manila, a pioneer program in graduate

health informatics education. Together with

other physicians and health workers and withthe help of Pasay City health department,

he helped create and manage the Commu-

nity Health Information Tracking System or

CHITS, a multi-awarded IT application and

the Philippines rst electronic medical record

system for rural health clinics.

He has worked in various projects that

used IT as a tool for beer information man-

agement and has been an advocate of the use

of free and open source soware in the in-

formation systems in public service. In 2005,

because of his work in the use of open source

soware in his community health-based

projects, Marcelo was awarded by the Phil-

ippine Jaycees as one of the Ten Outstand-

ing Young Men in the eld of medical/health

information.

Aer serving in dierent positions in the

state University and various non-government

projects, he served as the director of the Na-

tional Telehealth Center, the pioneer research

and development center on the use of ICT for

health and development. He now serves as

chief information ocer (CIO) of PhilHealth.

Marcelo nds that even though he remains

a consultant at the Division of Trauma un-der the Department of Surgery at UP-PGH,

he does not practice surgery in the strictest

sense anymore. But he sees surgery at the

core of what he does in terms of diagnosing

a problem, craing a solution and thinking

of what problems he will encounter, during

and aer.

I think the surgical training contributed to

the discipline I needed to be CIO, he said.

Approaching a problem as a team and

having a leader to determine the plan of ac-

tion to solve the problem are some of thesimilarities between the practice of surgery

and informatics. But Marcelo thinks that

in surgery the roles are predetermined, in

contrast to informatics where the roles are

not yet clear.

While operating, you presume [team

members] are carrying out their tasks as you

have agreed upon. The good thing about sur-

gery is that all of these roles are pre-deter-

mined (meaning most everyone know what

theyre supposed to do by tradition). In infor-

matics, these things are not yet explicit and

must be explicated. But were geing there,

he said.

He thinks that the Philippines, while late

in adopting eHealth, is now in golden period

where the benets of IT can be maximized

to improve eciency in the delivery of care.

Marcelo opined that the government needs

to create an enabling environment to take ad-

vantage of this opportunity where costs of

ICT have gone down, people are IT-aware,

and almost everyone is already open to the

benets of ICT in health.

That is what I want to achieve right

now the creation of that environmentwhere the many potential players of eHealth

in the country (government, private sec-

tor, academe, NGO, patients, etc.) can

collaborate and create systems and sub-

systems that make for more aordable qual-

ity health care especially for the poor,

he said.


22/48


Hypoglycemia in the emergency room

TREATMENT FOCUS: Endocrinology and nephrology

Dr. Adrian Paul Rabe

Diabetes mellitus (DM) has profound ef-fects on small and large vessels, causingmicrovascular and macrovascular complica-

tions. Aside from these chronic problems, di-

abetes also causes other conditions that haveto be recognized and treated rapidly, known

as diabetic emergencies. These are diabetic

ketoacidosis, hyperglycemic hyperosmolar

state and hypoglycemia. Among the three,

hypoglycemia is considered to be the most

dangerous. Recently, hypoglycemia, dened

as blood sugar 70 mg/dL, was touted as one

of the reasons for the controversial exit of for-

mer Chief Justice Renato Corona during theimpeachment trial.

The paradox of hypoglycemia in diabetes

Since diabetes is a disease of elevated blood

sugar, patients oen ask why they are at risk

for hypoglycemia. The answer is actually sim-

ple: these patients receive medications that

lower blood sugar. Harrisons Principles of In-

ternal Medicine (HPIM, 18th edition) reportsthat hypoglycemia is most commonly a re-

sult of the treatment of diabetes.

The main risk factors of hypoglycemia in

diabetes are related to relative or absolute in-

sulin excess. Errors in insulin administration,

poor or erratic glucose intake, alcohol intake

(that reduces liver production of glucose) and

renal failure (that reduces insulin clearance)

are likely causes of low blood sugar.

Dr. Aldrin Loyola, an expert in adult medi-

cine from the University of the Philippines

Philippine General Hospital, adds that

hypoglycemia is further exacerbated when

the defenses of the body against low bloodsugar are compromised. The rst defense is

decreased insulin production that prevents

uptake of glucose from the blood, while the

second defense is increased glucagon which

stimulates glucose production. The third de-

fense is epinephrine, which increases liver

and kidney production of sugar. If blood sug-

ar still remains low, cortisol and growth hor-

mone are released to increase glucose produc-tion further and decrease glucose utilization.

Clinical clues to hypoglycemia

When sugar is still above 50 mg/dL, the

body develops signs and symptoms that sig-

nal the patient that blood sugar is danger-

ously low. Adrenergic symptoms include pal-

pitations, tremors and anxiety. On the other

hand, sweating, hunger and paresthesias areconsidered cholinergic symptoms.

Patients with diabetes may have aenua-

tion of these responses due to a reduced sym-

pathoadrenal response. This situation where

the patient does not recognize the hypoglyce-

mia episode is called hypoglycemia unaware-

ness.

If the blood sugar remains uncorrected and

dips below 50 mg/dL, diabetics develop neu-


23/48


roglycopenic symptoms from glucose depri-

vation of the brain. These include behavioral

changes, seizures and decreased states of con-

sciousness.

Loyola says that the diagnosis of hy-poglycemia is confirmed through the pres-

ence Whipples triad, comprised of symp-

toms of hypoglycemia, low plasma glucose

(not a capillary blood glucose determina-

tion), and relief of symptoms after plasma

glucose is raised.

Thus, if possible, given the patients cir-

cumstances and urgency, blood must be

drawn for examination before any eorts to

increase sugar.

Reversing hypoglycemia

The rst-line treatment of hypoglycemia is

oral administration of glucose. Glucose tab-

lets, glucose-containing uids, candy or even

food may be given as long as the patient is

able to take those forms of sugar.

Because of the risk of aspiration, patientswith neuroglycopenia should receive paren-

teral therapy. A bolus of 25 g of glucose may

be given intravenously (IV). A commonly

supplied form of parenteral glucose would

be a vial of D50-50, which contains 25 g of

glucose in 50 mL of sterile water. Such an IV

bolus should be given slowly to minimize ir-

ritation of the vein.

If glucose is not raised by these measures,parenteral glucagon may be given using a

1-mg dose. The action of this hormone is to

promote glycogenolysis, thus rendering it fu-

tile in patients with depleted glycogen stores.

Loyola warns that glucagon also causes a re-

actionary increase in insulin which may pro-

voke further hypoglycemia, which decreases

its value in Type 2 DM. Thus, one should con-

sider these factors before deciding to give glu-

cagon.Once glucose is raised, an IV drip of glu-

cose may be started to stabilize glucose con-

centrations. Tapering and adjustment of this

drip is dependent on serial glucose measure-

ments, which may be done using capillary

blood glucose.

Doing hypoglycemia justice

Aer stabilizing the patient, further inves-tigation as to the cause of the hypoglycemia

may be performed especially if the low sugar

is not explainable simply by poor intake, or

medications.

C-peptide levels measure insulin produc-

tion by the body and may be elevated in pa-

tients with Insulinoma. Critical illnesses, such

as sepsis or heart failure, are second to medi-

cations as the cause of hypoglycemia. Alcoholcauses low blood sugar, usually aer a sever-

al-day binge during which there is very lile

intake of food.

Loyola adds that other drugs are associ-

ated with hypoglycemia, such as angiotensin-

converting enzyme inhibitors, angiotensin

receptor blockers, beta-adrenergic receptor

blockers, quinolones and sulfonamides.

Clinicians thus have to be vigilant aboutthe signs and symptoms of hypoglycemia

especially among diabetics. Prompt recog-

nition and treatment are ways we could do

justice to these individuals with low blood

sugar.


24/48


The risks involved in kidney donation

Dr. Adrian Paul Rabe

Kidney donation is a prickly issue due tocertain ethical considerations. It must beperformed without seeking to dehumanizethe donor and devalue the act of donation,as recognized by Dr. Beatrice Concepcion, atransplant nephrologist from Makati Medical

Center and Medical Center Manila.Potential living donors should voluntarily

oer to donate their kidney. They may not becoerced nor are they allowed to receive anymonetary compensation. In the Philippines,there must be an established relationship be-tween the living donor and the recipient, beit by blood or an emotional relationship,shared Concepcion

A donor advocate may be recruited dur-ing decision making to ensure that a fully in-formed consent was taken, usually with fam-ily members taking part. All throughout theprocess of donation, counseling should alsobe performed.

These measures ensure that there would beno exploitation in organ donation. In contrast,other countries allow altruistic donationsaside from directed donations.

Rigorous donor Selection

Donor assessment is a meticulous process,taking 4 to 8 weeks. ABO compatibility (+/- HLAsensitization) is conrmed to initiate assess-ment. A complete history and physical examina-tion must be performed to detect subtle signs ofdisease, including a risk assessment for tubercu-losis, malaria, hepatitis virus and HIV.

Diagnostic regimen should be able to screen

subclinical diseases that adversely aect dona-tion outcomes. Results of tests are analyzed

with the clinical examination to create a globalassessment of the donor, which determineswhether or not donation can proceed.

Post-donation careThe immediate post-operative survival of

donors approaches that of any surgical proce-

dure under general anesthesia, with mortalityat 0.03 percent.

The most prominent problem is usuallypost-operative pain so they are usually senthome on pain medications. Practices varydepending on the transplant center but do-nors can be discharged a few days aer dona-tion, notes Concepcion.

Follow-up consults of donors are done at 2

weeks, 1 month and 6 months. Concepcion re-iterates, Donors who were screened appro-priately prior to donation do very well, withexcellent kidney function many years aertransplantation.

Donating improves donor survival?

Surprisingly, studies have shown asmall reduction in mortality for kidneydonors. This is aributable to the more

conscientious eorts made by donors tomaintain their health aer the loss of one kid-ney, including a balanced diet and exercise toprevent diabetes, hypertension, and obesity.One of the specic lifestyle recommendationsis to avoid contact sports, as well as excessiveintake of NSAIDs.

Donation is an option of growing importancein the Philippines. A well-informed orientationto this process will help encourage living do-

nors to give a part of themselves, in order to savea life.

TREATMENT FOCUS: Endocrinology and nephrology


25/48


Conference Calendar

July

3rd

National Prosthetics and Orthotics ConventionJuly 4-6, 2012Ino: Philippine Academy o Rehabilitation MedicineTelephone: (02) 536 9605Email: [email protected]: Manila Hotel, Manila

65th Annual Convention of the PhilippineAssociation of Nutrition

July 9-10, 2012Ino: Philippine Association o Nutrition, Inc.Cellphone: (0920) 286 1532Email: [email protected]: http://pan.nri.dost.gov.phVenue: Dusit Thani Ayala Center, Makati City

UPCOMING10th Surgical Forum, Philippine Society ofGeneral Surgeons

August 1-4, 2012Ino: Philippine Society o General SurgeonsTheme: Redefning General SurgeryTelephone: (02) 456 8411Email: [email protected]

Website: http://www.psgs.org.phVenue: SMX Convention Center

Philippine College of Chest Physicians Midyear

Convention 2012

August 2-4, 2012Ino: Philippine College o Chest PhysiciansTelephone: (02) 924 9204Email: [email protected]: http://www.philchest.org

Venue: Legend Hotel, Puerto Princesa, Palawan

Psychological Association of the Philippines49th Annual Convention

Hosted by University o San Carlos

August 15-17, 2012

Ino: Psychological Association o the Philippines

Telephone: (02) 453 8257

Email: [email protected]

Website: http://www.pap.org.ph

Venue: Waterront Hotel, Cebu City

13th Philippine Society of Allergy, Asthma

and Immunology Biennial Convention

September 3-4, 2012

Ino: Philippine Society o Allergy, Asthma

and Immunology

Telephone: (02) 712 9432


Venue: Softel Philippine Plaza, Pasay City

7th Biennial Convention, Society of Adolescent

Medicine of the Philippines

September 3-4, 2012

Ino: Society o Adolescent Medicine o the Philip-

pines

Cellphone: (0947) 844 4318 or (0928) 507 5724


Website: www.samphilippines.com

Theme: State o the Nations Adolescents

Venue: Diamond Hotel, Manila

Conference CalendarConference Calendar


26/48


A s we age, normal physiological changes occur, includ-ing atrophy of heart muscles, calcication of heartvalves and loss of elasticity of blood vessels. Changes in the

heart capacity result in reduced blood ow and decreased

stamina, reduced renal and hepatic function and less cellular

nourishment, and impaired blood pressure. Filipinos who are

40 years old and up are at risk of hypertension and lipid prob-

lems, which also increases the risk of heart disease.

Maintaining a healthy diet along with regular physi-

cal activity could prevent an estimated 80 percent of pre-

mature heart diseases and strokes.

Adding to the benets of lifestyle modication, Centrum Silver contains required amounts of

vitamins and minerals to support the cardiovascular health of adults aged 50 and up. It contains

beta-carotene, selenium, and vitamins C and E are antioxidants that control free radical damage;

and B vitamins such as folic acid and B6

and B12

that help in the regulation of plasma homocyste-

ine levels to decrease the risk of atherosclerosis and other cardiovascular problems.

Philips launches latest ultrasound system

Centrum Silver promotes cardiovascular health in older adults

P hilips, a world leader in healthcaresolutions, is raising the bar for med-ical imaging with the Philippine launch

of its latest ultrasound systemthe

iU22 xMatrix with Vision 2012 upgrade.

The technology delivers enhanced ul-

trasound image quality, allowing doc-

tors to gather more precise informationand give more condent diagnoses.

The Vision 2012 features next generation 2D, 3D and 4D performance enhancements as well as

an array of high-level imaging functions. The Auto Doppler capability automates repetitive manual

tasks to speed up and simplify standard vascular exams, while the Philips Fetal Heart Navigator

allows doctors to acquire the fetal heart volume in as lile as two seconds. The Vascular Plaque

Quantication (VPQ) on the other hand is a non-invasive tool that uses 3D technology to examine

the arteries and determine whether or not a patient is at risk of stroke or cardiovascular disease.

Photo shows Cellinjit Bhuel, Ultrasound Clinical Applications Specialist for Philips Ultra-

sound in Southeast Asia, explaining in detail the functions and upgrades of the Philips iU22xMatrix ultrasound.

MARKET WATCH


27/48

27 July 2012 Conference Coverage

Promising drug combination benefits

HER2+ breast cancer patients

48th Annual Meeting of the American Society of Clinical Oncology, 1-5 June, Chicago, Illinois, US

Radha Chitale

Anovel agent linking the antibody trastu-zumab (Herceptin) to a potent chemo-therapy drug improved progression free sur-vival in women with HER2-positive (HER2+)

metastatic breast cancer compared with stan-dard therapy, according to interim resultsfrom the phase III EMILIA* trial.

The new agent, called T-DM1, may alsohave positive implication for overall survival.

T-DM1 is a brand new way of treatingHER2+ breast cancer, said lead researcherDr. Kimberly Blackwell, Duke UniversityMedical Center in Durham, North Carolina,US. I think it is the rst of many antibodydrug conjugates to follow that will link a po-tent anti-cancer agent to the targeted deliverysystem of an antibody.

The trial, supported by Genentech, in-cluded 978 women with conrmed HER2+metastatic breast cancer who were on or hadrecently been treated with taxane and trastu-zumab.

Patients were randomized to infusions of

the HER2 antibody trastuzumab linked to themicrotubule inhibitor emtansine (trastuzum-ab emtansine, T-DM1) or oral lapatinib pluscapecitabine. Median follow-up was just over1 year for both groups.

Median progression free survival improved35 percent with T-DM1, 9.6 months versus6.4 months with lapatinib plus capecitabine(P


28/48


Radiation therapy in childhood increases

breast cancer risk

Radha Chitale

Adult survivors of childhood cancerstreated with radiation therapy have anincreased risk of breast cancer, similar to that

of women who carry BRCA gene mutations,even if the radiation dose was low.

Prior studies showed girls treated with

radiation to the chest have increased risk of

breast cancer, but lead researcher Dr. Chaya

Moskowitz, Memorial Sloan-Keering Can-

cer Center in New York City, New York, US,

said the comparison to risk from BRCA gene

mutations is unknown.

The researchers compared 1,268 female 5-yearcancer survivors from the Childhood Cancer

Survivor Study (CCSS) and 4,570 rst-degree fe-

male relatives of women with breast cancer from

the Womens Environmental Cancer and Radia-

tion Epidemiology (WECARE) to estimate the

incidence of BRCA-1 and -2 carriers.

The rate of breast cancer in the general

public was 4 percent by age 50, according to

analysis of the Surveillance, Epidemiology,and End Results (SEER) study.

Among the WECARE cohort, 324 women

were diagnosed with breast cancer by median

age 55. Cumulative incidence of breast can-

cer was 31 percent among those with BRCA-1

mutations and 10 percent among those with

BRCA-2 mutations.

In the CCSS cohort, 175 were diagnosed

with breast cancer at median age 38 with

a median 23 years lag until diagnosis. Me-

dian follow up of study participants was 26years.

The overall incidence of breast cancer was

24 percent among girls who survived any type

of cancer but the incidence among Hodgkins

lymphoma (HL) survivors was 30 percent by

age 50, similar to that of women with BRCA-1

mutations.

Moskowitz said the discrepancy could be

the result of a larger area of the chest exposedto radiation during treatment for HL, which

increases the risk of breast cancer.

Typically, people who receive radiation

doses of 20 Grays (Gy) or more are currently

recommended for cancer screening.

However, Moskowitz said it was remark-

able that women treated for cancers other

than HL with moderate doses of radiation

(10-19 Gy) to large areas of the chest also haveelevated risk of breast cancer similar to that of

BRCA-2.

These women are not currently recom-

mended for screening but Moskowitz sug-

gested they would benet from breast cancer

surveillance strategies as their risk is higher

than previously recognized.



29/48


Elvira Manzano

Two relatively new drugs for patientswith recurrent or metastatic breast can-cer failed to beat old stand-by paclitaxel in aphase III cooperative group trial.

Treatment with paclitaxel resulted in a lon-

ger median progression-free survival (PFS) of

10.6 months compared with 9.2 months and

7.6 months for novel nanoparticle albumin-

bound paclitaxel (nab-paclitaxel) and ixabep-

ilone, respectively. Rates of peripheral neu-

ropathy and hematologic toxicity were also

higher with both agents than with paclitaxel.Neither weekly nab-paclitaxel nor ixabep-

ilone is superior to weekly paclitaxel, said

study author Dr. Hope Rugo, of the Univer-

sity of California, San Francisco, US. In com-

bination with bevacizumab, weekly paclitaxel

is the beer tolerated drug.

The study involved 799 patients with lo-

cally advanced or metastatic breast cancer

and no prior chemotherapy randomized tonab-paclitaxel 150 mg/m2, ixabepilone 16 mg/

m2), or paclitaxel 90 mg/m2 (as a control) plus

bevacizumab every 2 weeks. Each treatment

cycle lasted for 3 weeks, followed by a 1-week

break. The primary endpoint was PFS or time

from randomization to disease progression or

death from any cause. Median follow-up pe-

riod was 12 months. The study was powered

to detect a hazard ratio of 1.36 (median PFS of10 vs. 13.6 months).

Ixabepilone was dropped earlier from the

trial aer it demonstrated signicantly worse

PFS. Our data showed that we should not

simply assume that newer drugs are always

beer than the standard therapies for meta-

static breast cancer, said Rugo. She explained

that dosing schedules are constantly being

examined and rened, new therapies tested,and molecular characteristics of tumors are

looked at closely to determine the right treat-

ment for the right patient, with least toxicities.

However, she said nab-paclitaxel may be

a useful alternative in patients who cannot

tolerate paclitaxel or in a seing where pacli-

taxel is not readily available.

The US Food and Drug Administration in

November 2011 revoked bevacizumabs con-ditional approval as a treatment for metastat-

ic breast cancer because of potentially serious

side eects such as high blood pressure and

hemorrhage. At that time, enrolment for the

trial, called CALGB 40502/NCCTG N063H,

had already started.

Newer agents no better than paclitaxel as

first-line breast cancer therapy



30/48


Christina Lau

Afatinib, an investigational drug that ir-reversibly blocks EGFR (ErbB1), HER2(ErbB2), HER3 (ErbB3) and HER4 (ErbB4),

signicantly extended progression-free sur-vival (PFS) vs the pemetrexed/cisplatin com-

bination in LUX-Lung3 the largest and most

robust phase III trial so far in EGFR mutation

positive advanced lung adenocarcinoma.

The oral pan-ErbB inhibitor was particu-

larly benecial for patients with deletion 19

or L858R common mutations that together

accounted for 89 percent of all EGFR muta-

tions in the trial.Unlike reversible EGFR tyrosine kinase

inhibitors such as getinib and erlotinib,

afatanib blocks the entire ErbB family of re-

ceptors permanently, said lead author Dr.

James Yang of the National Taiwan Univer-

sity Hospital. While getinib and erlotinib

has demonstrated signicant benet vs rst-

line chemotherapy, LUX-Lung3 is the rst

trial in EGFR mutation positive lung cancer touse pemetrexed/cisplatin as a chemotherapy

comparator.

The global trial included 345 treatment-na-

ve patients from 25 countries who had stage

IIIB (wet) or IV disease (median age, 61 years;

ECOG performance status, 0-1; East Asians,

72 percent; never-smokers, 68 percent). Pa-

tients were randomized 2:1 to receive afatinib

(40 mg) daily or pemetrexed (500 mg/m2) plus

cisplatin (75 mg/m2) q21d until progression.

The trial met its primary endpoint of

PFS. Aer a median follow-up of 8 months,

patients receiving afatinib had a signicant4.2-month improvement in PFS. Median PFS

was 11.1 months with afatinib vs. 6.9 months

with pemetrexed/cisplatin [hazard ratio

(HR) 0.58; P=0.0004], Yang reported. The

12-month PFS rate was 47 vs. 22 percent.

Importantly, the PFS benet of afatanib

was consistent in all relevant subgroups, in-

cluding gender, age at baseline, race (Asian

or non-Asian), baseline ECOG performancestatus, and smoking history (never smoked,

or smoked 1 year).

The benefit of afatinib was even great-

er in patients with deletion 19 or L858R

[N=308], he continued. In these patients,

afatinib doubled PFS to 13.6 months vs.

6.9 months with pemetrexed/cisplatin [HR

0.47; P


31/48


In addition, afatinib signicantly pro-

longed the time to deterioration of cough (HR

0.6; P=0.007) and dyspnea (HR 0.68; P=0.015).

Patients treated with afatinib had beer qual-

ity of life.Grade 3/4 adverse events that were in-

creased with afatinib include diarrhea [14.4

vs. 0 percent], rash/acne [16.2 vs. 0 percent],

stomatitis/mucositis [8.7 vs. 0.9 percent], par-

onychia [11.4 vs. 0 percent], and dry skin [0.4

vs. 0 percent], said Yang. These adverse

events were as expected with EGFR-targeting

therapies, and were manageable and revers-

ible. It is also important to note that patients

in the afatinib arm received 16 cycles of ther-

apy, vs. 6 cycles in the pemetrexed/cisplatinarm.

In LUX-Lung3, only 7.9 percent of patients

discontinued afatinib due to treatment-related

adverse events (vs. 11.7 percent with peme-

trexed/cisplatin), and only about 1 percent dis-

continued the drug due to diarrhea.

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32/48


Christina Lau

The multi-kinase inhibitor regorafenib mayrepresent the rst targeted treatment op-tion for patients with metastatic and/or unre-

sectable gastrointestinal stromal tumor (GIST)whose disease progressed despite prior use of

both imatinib and sunitinib, suggest results of

a phase III international trial.

The GRID (Regorafenib in Progressive

Disease) trial included 199 patients from 17

countries who failed at least imatinib and

sunitinib the only two drugs approved for

GIST worldwide. Patients were randomized

to receive either regorafenib 160mg once dai-ly plus best supportive care (BSC) (N=133),

or placebo plus BSC (N=66), on a 3-weeks-on

1-week-o schedule. The trial was unblinded

on disease progression, when placebo-treated

patients were eligible for crossover to open-

label regorafenib and regorafenib-treated pa-

tients were continued on the active treatment.

On the next progression, patients were taken

o treatment.The trial met its primary endpoint, as pro-

gression-free survival (PFS) was signicantly

and four times longer in the regorafenib arm.

Median PFS was 4.8 months for regorafenib

vs. 0.9 months for placebo, with a hazard ratio

(HR) of 0.27 (P


33/48


from 3-6 months to 5 years or more, 85 to 90

percent of patients ultimately develop resis-

tance to these tyrosine kinase inhibitors (TKIs)

that target KIT or PDGFRA. Regorafenib is

a structurally distinct oral inhibitor of KIT,

VEGFR-1, murine VEGFR-2, PDGFR-, RET,

BRAF and FGFR-1 that appears to target

GIST in a possibly more powerful way, mak-

ing it a potentially signicant new option to

help patients.


34/48


Christina Lau

Adolescents and young adults with high-risk acute lymphoblastic leukemia (ALL)have poorer survival and higher toxicity from

treatment than their younger counterparts,

according to new data from a major phase

III study which highlights the need for beer

treatment strategies for this group of patients.

Historically, ALL patients older than 16

years have an inferior outcome compared

with patients aged 1 to 15 years because older

patients have higher rates of relapse and tox-

icity, said lead author Dr. Eric Larsen of the

Maine Childrens Cancer Program in Scarbor-

ough, Maine, US. In the Childrens Oncology

Group (COG) study ALL0232, we tested dexa-

methasone vs. prednisone during induction

and high-dose methotrexate vs. escalating

Capizzi methotrexate plus PEG asparaginase

during interim maintenance 1 in a 2 x 2 fac-

torial design. For the st time, patients aged

21-30 years were eligible for enrollment in an

ALL study.ALL0232 was in patients with newly-diag-

nosed B-precursor high-risk ALL. Of a total of

2,571 eligible patients in ALL0232, 501 (20 per-

cent) were adolescents and young adults aged

16-30 years. This represents the largest cohort

of adolescent and young adult ALL patients to

date in a single clinical trial, he said. Previ-

ously, observations about ALL outcome were

usually made by comparing one trial with an-

other. In ALL0232, the number of patients re-

ceiving the same treatment was large enough

to allow comparison within the same trial.

At 5 years, ALL0232 patients aged 16-30

years had signicantly poorer event-free sur-

vival (EFS) and overall survival (OS) than

those


35/48


P


36/48


Radha Chitale

Cancer patients may live longer if theirtumor microenvironment is normalized,rather than starved of blood and other nutri-

ents, so that therapeutic treatments are more

eective, said Professor Rakesh Jain, of the

Steele Lab for Tumor Biology, Massachuses

General Hospital, Harvard Medical School in

Boston, Massachuses, US.

This approach has implications for the half

billion people worldwide with diseases char-

acterized by abnormal vessels, he said.

As tumors grow, vessels can become disor-

ganized, misshapen or blocked, creating areas

without oxygen. This hypoxic environment

creates high interstitial uid pressure and

contributes to genetic instability, angiogen-

esis, resistance to cell death and metastasis.

However, chemotherapy, radiation therapy

and immunotherapy are demonstrably more

eective when the tumor microenvironment

is in a normal state.

In a study of 30 patients with recurrentglioblastoma treated with an anti-vascular

endothelial growth factor (VEGF), seven had

increased tumor blood perfusion for more

than 1 month, which was associated with

increased survival of 6 months compared to

patients in whose tumors blood perfusion

remained stable or decreased (P=0.019). [Can-

cer Res 2012;72:402-407]

Normalization induced blood ow hasthe potential to increase survival in patients,

Jain said.

However, dose maers when treating with

anti-VEGF therapy to improve blood ow to

tumors; too lile anti-angiogenic agent results

in no change to the blood vessels and too much

leaves only a small window for normalization

before excessive pruning and hypoxia set in.

Smaller molecules, about 10 nm, were the

optimal size for drug delivery to promote

normalization and tumor response.

Alleviating hypoxia in tumors makes the

mass immunostimulatory, Jain said, and ves-

sels are able to bring more T-cells to the tumorto increase the ecacy of immunotherapy.

Five to 10 years from now we would see

normalization be combined with a variety

of immunotherapies, he said.

Jain also noted that a similar normalization

strategy could be used for lymphatic vessels

and the tumor cellular matrix as well to im-

prove perfusion and improve the ecacy of

chemotherapy, radiation therapy and immu-notherapy and overall survival.

Feeding, not starving, tumors improves

response to therapies and overall survival


Normalizing the tumor microenvironment may help enhance the ecacy

of therapeutic treatments.


37/48


Radha Chitale

Disrupted manufacturing and qualitycontrol are the main culprits behind thehigh volume of drug shortages in the US that

have le many cancer patients without neces-

sary treatment.

Dr. Richard Schilsky, of the University of

Chicago and chair of the ASCO Government

Relations Commiee, described recent un-

precedented shortages of generic injectable

drugs such as methotrexate that are main-

stays of treatment for many cancers.

Were never exactly sure when a generic

drug is suddenly going to go out of supply,

he said, which creates anxiety for patients

and treatment planning diculty for physi-

cians.

Hundreds of drugs have been in short sup-

ply in the US over the past year including

methotrexate, used frequently for leukaemia,

Doxil, which treats ovarian cancer, paclitaxel,

used in a variety of cancers including breastcancer, mustargen, used to treat lymphoma,

and uorouracil, given for colorectal and

other cancers, and is a key part of adjuvant

therapy.

Shortages appear to be most acute among

community practices, where the majority of

adults receive care, said Dr. Michael Link,

of the Lucile Packard Childrens Hospital at

Stanford University in California, US andASCO president.

Acute cancer drug shortages due to

manufacturing, quality control


Dr. Sandra Kweder, deputy director of the

Oce of New Drugs at the US Food and Drug

Administration (FDA), said disruptions at

large manufacturers of sterile injectable drugs

have the most impact. For example, closing a

single facility that makes 30 drugs can lead to

dozens of shortages.

Contamination with glass or metal parti-

cles in vials of medicine can also compromise

drug availability.

Kweder said the FDA works with drug

manufacturers to address shortages by en-

couraging early reporting of production di-

culties so that the agency can source the same

or alternative drugs from dierent compa-

nies, sometimes from overseas manufacturers

in India or Australia, for example.

Schilsky noted that cancer drug shortages do

not appear to be a problem in overseas markets.

Permanent solutions to drug shortages will

likely require legislation to make 6 months no-

tice for withdrawals or manufacturing inter-

ruption mandatory by drug companies, with

penalties for non-reporting, Schilsky said.Dr. W Charles Penley, of Tennessee Oncol-

ogy in the US and incoming chair of the ASCO

Government Relations Commiee, noted that

drug shortages, particularly of widely used

generics, impact clinical research as doctors

are unable to use them as standard therapy to

measure experimental drugs against.

This could really slow down progress if

we dont have access to these very standardand vital agents, he said.


38/48


Elvira Manzano

Adding bevacizumab to standard che-motherapy delayed cancer progressionin women with platinum-resistant ovarian

cancer, results of a phase III AURELIA* trial

showed.

Median progression-free survival (PFS)

a primary endpoint of the study was 6.7

months for combination therapy compared

with 3.4 months for chemotherapy alone. The

objective response rate more than doubled

with the addition of bevacizumab 12.6 per-

cent to 30.9 percent (P=0.001).

For the rst-time in platinum-resistant

ovarian cancer, we have been able to signi-

cantly improve progression-free survival with

a combination therapy, said lead study au-

thor Dr. Eric Pujade-Lauraine, professor, Uni-

versit de Paris Descartes, France and head of

the Group dInvestigateurs Nationaux pour

lEtude des Cancers Ovariens (GINECO),

a clinical trials cooperative group based in

France. The risk of the disease geing worsewas halved in patients treated with the com-

bination therapy. This is a breakthrough and

will denitely change the practice in treating

patients with ovarian cancer.

In the study, 361 women with epithelial

ovarian, fallopian tube or primary peritoneal

cancers that had not responded to platinum-

based chemotherapy were randomized to

receive standard chemotherapy or bevaci-zumab plus chemotherapy (with one of three

standard chemotherapy agents topotecan,

liposomal pegylated doxorubicin or weekly

paclitaxel). Secondary endpoints were ob-

jective response rate, overall survival, safety,

and quality of life.

Aer a median follow-up of 13.5 months,

91 percent of patients in the chemotherapy-alone group had progressed compared with

75 percent in the combination therapy group.

The dierence translated into a 0.48 hazard

ratio of progression (P


39/48

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LINKING PEOPLE, POTENTIAL AND PROGRESS

On the week of the Singapore F1 we are holding HIMSS AsiaPac12. It is the onehealthcare IT event dedicated to connecting people and information in new ways to

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39 July 2012 In Pract ice

Therapeutics in osteoporosis: What every

GP should know

Associate Professor Leong Keng HongConsultant Rheumatologist,

Gleneagles Medical Centre, Singapore

Adjunct Associate Professor,

Yong Loo Lin School of Medicine,

National University of Singapore

Osteoporosis: A silent epidemic

Osteoporosis oen called a silent disease is

characterized by a low bone mass and deterio-

ration of the bone tissue, leading to enhanced

bone fragility and a consequent increase in

fracture risk. The condition primarily aects

post-menopausal women, but may also aect

elderly men.

Bones undergo continuous remodelling

through repeated cycles of destruction and

rebuilding to prevent accumulation of bone

microdamage. Osteoclasts and osteoblasts

sequentially carry out resorption of old bone

and formation of new bone. In the elderly

and in post-menopausal women, the extent of

bone resorption far exceeds bone formation,

resulting in bone loss. If this continues over

the years, the result is osteoporosis.Approximately 200 million women world-

wide suer from osteoporosis. It is estimated

that by 2050, half of all fractures in the world

will occur in Asia. In Singapore, the incidence

of hip fractures rose ve-fold to 403 cases per

100,000 in women >50, or eight times more

than the breast cancer cases.

Aside from hip fractures, the most com-

mon clinical outcomes of osteoporosis arefractures of the spine, pelvis, upper arm and

wrist. Of these, hip fracture is the most severe

as it is associated with poor or slow healing

aer a surgical repair.

Pathogenesis of osteoporosis

Inadequate peak bone mass and imbalances

in bone resorption and bone formation lead to

structural deterioration and eventually, osteo-

porosis. Lack of estrogen as a consequence ofmenopause increases bone resorption and de-

creases bone deposition. Calcium metabolism

may play an important role in bone turnover,

as well as deciency in calcium and vitamin D.

Diag

medical tribune july 2012 ph

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