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February 2013

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Fasting before lipid tests: An absolute requirement?

2 February 2013

Fasting before lipid tests: An absolute requirement?Rajesh Kumar

Fasting prior to routine blood lipid tests may be unnecessary, according to new research.

The findings have stirred a debate, with some physicians proposing to do away with the current guidelines that recommend mea-suring fasting lipid levels, while others are advising caution.

Earlier studies have suggested that non-fasting lipid profiles change minimally in re-sponse to food intake and may be superior to fasting levels in predicting adverse cardiovas-cular outcomes, said study authors Drs Da-vinder Sidhu and Christopher Naugler of the University of Calgary, Alberta, Canada. [Arch Intern Med 2012;172:1707-1710]

To confirm the findings in a large commu-nity cohort, they conducted a cross-sectional examination of laboratory data from 209,180 subjects, of whom 111,048 were women. The data included records of the subjects’ fasting durations, which ranged from 1 to 16 hours, and their lipid level measurements, over a 6-month period in 2011. Fasting time was stratified into hourly intervals from 1 to 16 and correlated with lipid results including mean high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, to-tal cholesterol (TC), and triglycerides (TG).

On analysis, the researchers found that the mean levels of TC and HDL cholesterol dif-fered little between individuals with various fasting times. Specifically, these levels varied by less than 2 percent for TC and HDL choles-terol, less than 10 percent for calculated LDL cholesterol, and by less than 20 percent for TG.

“This finding suggests that fasting for rou-

tine lipid level determinations is largely un-necessary,” said the researchers.

In an accompanying editorial, Dr. J. Mi-chael Gaziano of Brigham and Women’s Hospital, Harvard Medical School in Boston, Massachusetts, US, said the incremental gain in information of a fasting profile is exceed-ingly small for total and HDL cholesterol val-ues and likely does not offset the logistic im-positions placed on our patients, laboratories, and our ability to provide timely counseling to our patients.

“This, in my opinion, tips the balance to-ward relying on non-fasting lipid profiles as the preferred practice. Therefore, in practice, you can begin with a non-fasting lipid pro-file and [use it] for risk assessment, decisions about treatment and monitoring the effects of treatment,” Gaziano concluded, adding that some sample fasting may be useful.

Drs Amit V. Khera and Samia Mora, also of Brigham and Women’s Hospital and Har-vard Medical School, in their commentary, said that “a growing body of evidence from observational studies and statin clinical tri-als suggests that non-fasting or fasting blood draws may be used for cardiovascular risk assessment and therapeutic decisions, espe-cially when lipid sub-fractions other than LDL-C (eg, the total HDL-C ratio or non-HDL-C) are emphasized.”

“Additional prospective studies that di-rectly compare the association of fasting and non-fasting lipid levels with cardiovascular outcomes in the same individuals would be informative. Further validation studies are needed before a non-fasting lipid test-ing strategy is universally endorsed,” wrote Khera and Mora.

3 February 2013

Dr. Ho Kay Woon, cardiologist at the National Heart Centre Singapore, said that central to interpreting the study results is the premise that LDL is the primary target of treatment, as demonstrated in multiple, large, randomized trials and subsequent guidelines.

However, LDL value is not directly mea-sured in the common biochemistry laboratory but is derived using the formula: LDL = TC – HDL – TG/5.

“In subjects with TG levels more than 400mg/dL, LDL estimation by this method is not accurate. Of note, Sidhu and Naugler’s study excluded 1.5 percent of patients who had TG levels [higher] than 400 mg/dL, many of whom may be a result of not fasting before

lipid testing,” said Ho. “As diet affects TG levels up to 20 percent,

this significantly affects the accuracy of the derived LDL levels if a subject has not fasted. Indeed in this study, the variability of LDL with fasting can up around 10 percent. When taken in context that LDL needs to be closely monitored and treated to target, this variabil-ity of LDL without fasting does not provide a precise measurement for lipid management.”

Therefore, although the study showed interesting results with potential application of non-fasting lipid measurements, Ho did not foresee a change in the requirement for fasting lipid sample to accurately determine the LDL levels, which remains the current primary lipid treatment target.

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4 February 2013

Leonard Yap

The number of preterm births in 39 high-resource countries can be reduced with

some readily available treatments, and this could result in preventing 58,000 premature babies a year, says a group of international experts.

Preterm birth, defined as delivery before 37 weeks of completed gestation, is the lead-ing cause of newborn deaths. Babies who sur-vive early birth often face a lifetime of health challenges, including breathing problems, ce-rebral palsy, and motor and intellectual dis-abilities.

In addition to preventing preterm births, the economic cost-savings to the healthcare system could number in the billions. “Gov-ernments and health professionals in these 39 countries need to know that wider use of prov-en interventions can help more women have healthy pregnancies and healthy babies,” said lead author Dr. Hannah H. Chang, a consul-tant for The Boston Consulting Group (BCG), Boston, US. “A 5 percent reduction in the pre-term birth rate is an important first step.”

The article was published to coincide with the second annual World Prematurity Day. [Lancet 2012 doi:10.1016/S0140-6736(12)61856-X]

The authors listed five proven interven-tions which, when combined, could lower the rate of preterm births across the 39 countries from an average 9.6 percent of live births to 9.1 percent, and save about US$3 billion in health and economic costs:

• eliminating early cesarean deliveries and induction of labor unless medically neces-sary.

• decreasing multiple embryo transfers dur-ing assisted reproductive technologies.

• helping women quit smoking.• providing progesterone supplementation

to women with high-risk pregnancies.• cervical cerclage for high-risk women with

short cervix.“The means to reduce the risk of preterm birth by 5 percent are already available,” said Dr. Catherine Y. Spong, associate director for extramural research, Eunice Kennedy Shriver National Institute of Child Health and Hu-man Development, US. “Continued research into the causes of preterm birth has the poten-tial to reduce the proportion of infants born preterm even further.”

The significance of the 5 percent reduction builds on recommendations of the publica-tion Born Too Soon: The Global Action Report on Preterm Birth, which presented the first-ever preterm birth data for 184 countries and out-lined steps that all countries could take to help prevent preterm births and care for af-fected newborns.

About 15 million babies worldwide are born preterm each year and more than one million of these die as a direct result of their early birth. The US preterm birth rate ranks 131 out of 184 countries. [Born Too Soon: The Global Action Report on Preterm Birth. Available at: www.who.int/pmnch/media/news/2012/preterm_birth_report/en/index.html Accessed on 20 November]

Preterm births can be prevented

5 February 2013 Forum

Connecting the wireless health industryExcerpted from a presentation by Mr. John Stefanac, president of Qualcomm (South East Asia/Pacific), during the first Asia-Pacific Health Forum recently organized by ESSEC business school in Singapore.

More people today have access to a mobile device than they have to drinking water, electricity or a

toothbrush. Or dare I say proper medical care.Think about the way we acquire and read

books today compared with how we did 20 years ago. An average book holds just over 1MB of fixed data, with no access to new data. However, a Kindle can store over 3GB (ie, 3,000 times more data). Think of the way we purchase, listen to and share music, or even the way we search for and book travel com-pared with how we did 2 decades ago. And think of all of these capabilities finding their way into health care, an industry that to date is virtually untouched by the digital revolu-tion.

Health care is witnessing a big shift from what we call ‘sick care’ to ‘health manage-ment care.’ Current healthcare systems pay physicians, hospitals and caregivers for treat-ing sick patients, while the future reimburse-ment models will pay healthcare institutions and caregivers to keep people healthy and out of acute care settings. This shift in reimburse-ment models will keep patients healthier and significantly lower health care costs. And mo-bile health (mHealth) technology will play a huge role in this transformation.

One of the first examples of this shift is that from October 1, 2012, hospitals in the US are being held financially responsible for patient readmissions within 30 days. The ‘Medicare 30-Day Readmission Rule’ is causing hospi-

tals and healthcare facilities to look seriously at remote monitoring technologies to ensure their patients aren’t returning after being dis-charged.

This creates an opportunity for companies with mHealth solutions to engage with hospi-tals that earlier didn’t have a huge incentive to listen. Over the past few years, we have been helping to build an mHealth ecosystem by

Technology innovators continue to challenge the way things are done in healthcare.

6 February 2013 Forumconnecting the big companies, insurance pro-viders, pharmaceutical and medical device manufacturers, and technology corporations together.

A US$100 million Qualcomm Life Fund has also been set up to accelerate wireless health services and technology adoption. In-vestments will include: • biosensors or devices for vertically focused

applications like chronic disease care, med-ication compliance, and fitness or wellness;

• integrated system providers that do remote diagnosis, monitoring, or specialize in en-abling independent living;

• software health IT applications; and• health informatics/analytics.

But it’s also important for startups and in-novators to challenge the way things are done in health care. Already, innovative solutions have begun emerging that will help people stay healthy while facilitating easier manage-ment of chronic diseases – with seamless ac-cess to patient data for all those involved in care.

But there are still some issues that we need to overcome if we are going to see a successful mHealth industry. These include: lack of stan-dards and interoperability; multiple radios and operating systems; the devices’ poor bat-tery life and security concerns. The 2net plat-form is addressing some of those challenges. The 2net Hub is a plug-and-play wireless gateway device that connects medical devices to ‘cloud’ computing resources seamlessly and can address the complexity of multiple radios and operating systems.

It can push medical device and application data onto the cloud-based internet data re-pository so that data can be sent securely any-where it needs to go, be it to the hospital or family physicians. It can support Bluetooth, Bluetooth low energy, Wi-Fi, and ANT+ local

area radio protocols which cover the majority of low-power radio medical devices currently used.

By including all of these protocols, the hub alleviates the burden on health service pro-viders of selecting medical devices with only one type of radio. To meet healthcare security and privacy requirements, data will be com-municated using SSL secure communication and separately certified as Class-1 Medical Devices under the EU Directive 93/42/EEC (MDD) and US FDA listed as Class I Medical Device Data Systems (MDDS).

At the individual level, we will soon use our phones to communicate, manage our time, pay our bills, turn the thermostat at home on to the appropriate temperature as we’re leaving work, open our door when we get home, and, we believe, to eventually man-age and even diagnose our health with a new world of Internet of Medical Things.

New healthcare tools are now available that leverage wireless and mobility to allow consumers to take charge of their own health.

Some examples are: • Entra’s MyGlucoHealth Bluetooth blood

glucose meter that allows diabetics to transmit their blood sugar readings to the cloud-based internet data repository to bet-ter manage their disease;

• Asthmapolis wirelessly enabled asthma in-haler;

• Lifecomm 3G-enabled personal emergency response device to monitor the elderly, in-cluding motion sensors and voice recogni-tion and location capabilities; and

• A&D Medical’s Bluetooth enabled blood pressure cuffs, weight scales, and other health-related devices to manage chronic diseases and wellness. The time is truly ripe for a mobile health-

care revolution.

7 Philippine FocusFebruary 2013

Ona declares sin tax law as victory for Filipinos

Dr. James Salisi

D epartment of Health (DOH) secre-tary Dr. Enrique Ona declared the enactment of the Sin Tax Reform

Bill a victory for the health of the Filipino people when President Benigno Aquino III signed into law Republic Act 10351 or An Act Restructuring the Excise Tax on Alcohol and To-bacco last December 20, 2012. “The enactment of this law is a victory in our campaign to protect our people, espe-cially the young and the poor, from the ill effects of smoking and excessive drinking. With higher prices, the number of young and poor people smoking and drinking excessively will be reduced significantly, resulting in lower incidence of smoking- related non-communicable illnesses such as lung cancer, heart attack, strokes and chronic lung disease as well as diseases associated with excessive drinking such as liver diseas-es and trauma secondary to drunk driving,” Ona said. RA 10351 raises excise taxes on tobacco and alcohol products. From 2013-2016, it is esti-mated that the measure will rake in P184.31 billion in cumulative incremental revenue, of which an estimated P146.7 billion will be al-located for health. The funds generated by this law will be used to expand PhilHealth enrolment of the second poorest quintile of Filipinos, upgrade

hospitals and other health facilities and ex-pand preventive and promotive health pro-grams under the DOH’s Universal Health Program. Ona lauded legislators for passing the law. The bill that preceded it encountered stiff op-

position from tobacco lobbyist before the ver-sions of the House of Representatives and the Senate was passed. “The Department of Health is grateful for the invaluable dedication of Senator Franklin M. Drilon and Representative Isidro Ungab in ensuring that this critical health measure is passed,” Ona said. Eighty percent of the revenues generated by the excise taxes on tobacco and alcohol will go to health programs especially to enrol 5.6 million poor Filipinos to PhilHealth while the rest will go to tobacco farmers. “The Sin Tax Reform Law is the game changer that will drastically alter the land-scape of our health care system for the better and ensure the provision of modern, acces-sible and affordable health services for our people, the essence of Kalusugan Pangkalahat-an,” Ona said.

The enactment of this law is a victory in our

campaign to protect our people

‘‘

READ JPOG ANYTIME, ANYWHERE. Download the digital edition today at www.jpog.com


Bioinformatics software can identify hepatitis C virus subtypes

Dr. Carol Tan

I dentifying the subtypes of the Hepatitis C virus (HCV) can be accomplished using

different bioinformatics tools, according to a study recently published in the Philippine Journal of Science by Dr. Michael Baclig et al. from the Research and Biotechnology Division of St. Luke’s Medical Center. The study described the step-by-step process involved in identifying the three subtypes of HCV and compared the accuracy of using restriction fragment length polymorphisms (RFLP) analysis against the gold standard which is deoxyribonucleic acid (DNA) sequencing. In the study, samples of viral ribonucleic acid (RNA) were extracted from the blood of 30 patients who were positive for HCV. The RNA was subjected to reverse transcription and converted into complementary DNA (cDNA). Polymerase chain reaction amplification of the cDNA was performed, and the products underwent both DNA sequencing and addition of restriction enzymes to identify RFLPs. Of the 30 HCV positive samples, DNA sequencing identified 15 (50 percent) of the samples as subtype 1a, while the remaining 15 (50 percent) were classified as subtype 1b. In contrast, RFLP analysis identified 16 samples (53 percent) as 1a, 13 samples (43 percent) as 1b and one sample (4 percent) as mixed subtype (1a/1b). The predictive value of the RFLP analysis was 94 percent (15 out of 16 samples) for subtype 1a and 100 percent (13 out of 13 samples) for subtype 1b.

The study explained that RFLP analysis is an easy and rapid method for screening of HCV positive samples; however, DNA sequencing is still the gold standard for determining HCV subtypes. The authors emphasized that identification of HCV subtypes has multiple benefits. Knowledge of the prevalence of different subtypes provides a clue about HCV genomics, which is useful for epidemiologic studies. In addition, formulation of an effective vaccine against HCV is dependent on identifying HCV subtypes which infect human beings. Finally, from a clinical perspective, the management of patients positive with HCV is tailored depending on the subtype identified. The choice of antiviral medications prescribed to patients is adjusted depending on which subtype is present. The authors concluded that accurate identification of HCV subtypes may be done using bioinformatics software. This information can be utilized to generate many benefits in clinical, epidemiologic and public health settings.


Dr. Nicolo Cabrera

T he Department of Health (DOH) created a foreign surgical and medical mission

(FSMM) unit under the Bureau of Interna-tional Health Cooperation to facilitate imple-mentation of the Administrative Order No. 2012-0030, “Guidelines on Foreign Surgical and Medical Mission Program in Support of Universal Health Care/Kalusugan Pangkala-hatan.” Health secretary Dr. Enrique Ona recog-nized the role of FSMMs in meeting the ob-jectives of universal health care, especially when these activities provide necessary medical services to underserved communi-ties through partnerships between foreign individuals or organizations and a local government unit, non-governmental orga-nization, hospital or medical society. These activities may be conducted once or as part of an adopt-a-hospital program. The DOH maintained that these programs should complement existing government health programs. The DOH means to set up a monitor-ing and evaluation system for FSMMs con-ducted in the country. Local partners will be required to submit regular reports detail-ing their activities that will be used to as-sess and improve implementation of FSMM programs. The program’s success depends

largely on the cooperation and collaboration of different stakeholders such as the Profes-sional Regulation Commission, Department of Social Welfare and Development, Com-mission on Filipinos Overseas, Department of Interior and Local Government, local gov-ernment units and non-government organi-

zations. DOH statistics showed that 154 missions were conducted in 2011 in the National Capital Region as well as the provinces of Cebu, Bataan, Leyte, Batangas, Nueva Ecija, Pangasinan, Abra, Quezon and Sorsogon. The DOH noted that the challenges in these FSMMs were the identification of communi-ties that required missions the most, the lack of infrastructure for sustainable continuity of care and the need to expedite procedures for facilitation and coordination. The DOH is also in the process of de-signing a website to facilitate FSMM ap-plications. The text of the DOH guidelines may be downloaded off the DOH home- page at www.doh.gov.ph.

DOH creates unit overseeing foreign medical missions

The DOH means to set up a monitoring

and evaluation system for FSMMs conducted

in the country

‘‘


A young pioneer in the field of research

Dr. James Salisi

D r. John Mark Velasco was supposed to just take a break from clinical medicine when he started working

at the National Institutes of Health (NIH) in the University of the Philippines (UP)-Manila but it set him to an alternative path away from the clinics.

“I definitely needed a breather and a re-spite from clinical work and tried applying for some moonlighting jobs; and also for a job opening at the NIH, UP Manila in 2004, where I was accepted and worked under the then deputy head of NIH, Dr. Vicente Belizario Jr. I credit him for initially help-ing me appreciate research and view it as an alternative career path,” Velasco said.

Graduating with a degree in Biology in 1999 at the University of the Philippines-Vi-sayas in Miag-ao, Iloilo, Velasco was accepted to the UP College of Medicine year where he finished his medical degree in 2004. During his time in medical school, he claimed that he was more interested in surgery than in re-search.

“Initially, I was thinking of specializing in urology and took it as an elective since I was thinking that I can take over the medical prac-tice of my uncle, a urologist practicing at West Virginia, US. On hindsight, I don’t think I was really cut-out to become a surgeon. I was not really thinking that far ahead in terms of ca-reer during medical school,” Velasco recalled.

His stint at the NIH where he coordinated research projects being implemented then in various parts of the country helped him land a job as a research coordinator for the Armed

Forces Research Institute of Medical Sciences (AFRIMS) Virology Research Unit (PAVRU). In 2006, he became one of the founding mem-bers of PAVRU, which is under the Depart-ment of Virology of the United States Army Medical component-AFRIMS (USAMC-AF-RIMS) located in Bangkok, Thailand.

Velasco considers receiving a certificate of meritorious honor from AFRIMS for establish-ing “ties and collaborations with the medical command of the Armed Forces of the Philip-pines” as one of the accomplishments he is most proud of. “Together with our collabora-tors at the V. Luna General Hospital (VLGH), Armed Forces of the Philippines Medical Center (AFPMC), we reactivated the Depart-ment of Research and Training and created a

BEYOND CLINIC


nationally and internationally registered Eth-ics Review Board,” he recounted.

He also spearheaded the renovation of a BSL-2 molecular laboratory for influenza PCR, dengue PCR, and testing for multi-drug resistant organisms at VLGH. This labora-tory was inaugurated by the Philippine Sec-retary of Defense and the US ambassador in March 2011 and serves the needs of the Phil-ippine military population and their direct dependents.

Velasco is now the deputy head and research coordinator of PAVRU. Together with the country head, he coordinates and oversees USAMC-AFRIMS research projects and activities in Manila and Cebu. His work also involves communicating and maintain-ing good working relationships with Philip-pine government agencies, such as the De-partment of Health, and international NGOs based in the Philippines. He is also the AF-RIMS liaison officer for the US embassy and the Armed Forces of the Philippines Medical Command.

The career path that he has decided to take away from clinical work is not without diffi-culties. Velasco had to learn things on the fly especially when he joined PAVRU where he managed research projects and coordinated with different government and non-govern-ment agencies. But a positive attitude has helped him cope and perform well in his line of work.

“I don’t view them as difficulties but as challenges which provide me with opportu-nities for learning new things and further add to my skill-set. I constantly encounter many challenges which were not taught in the con-fines of the classroom or hospital and which are not even related to the field of medicine, such as management, administration, logis-tics, diplomacy and communication skills

or things which are novel or cutting-edge in the field of research and epidemiology such as biosecurity and electronic disease surveil-lance,” he said.

But there are much more to like in his job than to view as challenges, Velasco explained. The support from his supervisors and the flexibility to explore and pursue interests in his chosen field are few of the many things he enjoys about his job. Additionally, there are many travel opportunities and occasions to interact with a lot of interesting people who are decision-makers, leaders and experts in their respective fields. “The job is not routine and I am constantly challenged, learning new things every day,” he said.

In his free time, Velasco engages in differ-ent activities such as trying out new sports like dragon boat, swimming and biking, as well as volunteering at a local church. His job has also allowed him to finish his master’s degree in Public Health at UP Manila, a post-gradu-ate certificate in Emerging Infectious Disease Epidemiology at the University of Iowa, USA and a post-graduate diploma in Clinical Tri-als under the London School of Hygiene and Tropical Medicine, University of London Sys-tem. He is now taking his last modules for a Master of Science in Clinical Trials in London.

“I plan to focus more on the field of clinical trials and vaccinology. Sometimes due to the intricacies in research, it is easy to get lost in the minutiae and details in the design of pro-tocols. I want to be better equipped and pos-sess the necessary background to be able to ap-preciate the many facets of doing research and approach vaccinology and clinical trials from a more holistic perspective,” Velasco shared.

Velasco admitted to having second thoughts about his present career, that there were times he missed clinical practice and seeing patients. However, seeing that he is a


Dr. Carol Tan

P atients with systemic lupus erythe-matosus (SLE) have an increased in-cidence of psychological illnesses,

according to a study conducted by Dr. Geral-dine Racaza et al. from the University of the Philippines- Philippine General Hospital.

This finding is supported by the results of another study conducted by Dr. Robelle Tanangunan et al. from the University of San-to Tomas, which reported on the various cop-ing strategies employed by patients with SLE. Both studies elaborated on the psychological and emotional difficulties of having SLE.

The first study, which was a case-control study conducted in the Philippine General Hospital, aimed to evaluate if there was a significant increase in the incidence of anxi-

ety and depression among SLE patients com-pared to matched disease-free controls. The study involved 155 adult patients diagnosed with SLE using the American College of Rheumatology 1982 classification criteria and 155 healthy controls were interviewed in this study. These participants were given the Fili-pino version of the Hospital Anxiety and De-pression Score questionnaires to assess their levels of anxiety and depression. Rheuma-tologists independently assessed the patients’ disease activity. Statistical tests were also em-ployed to determine any association between anxiety or depression and severity of the disease activity.

Results of this study showed that patients with SLE had significantly increased inci-dence of anxiety and depression. Anxiety disorders were seen in 49 percent of those

Asian Lupus Summit, 29-30 November, EDSA Shangri-La Hotel, Mandaluyong City

Psycho-emotional symptoms observed in lupus patients

CONFERENCE COVERAGE

part of and doing something worthwhile that can help not just a few patients but a large population is enough for him to regret noth-ing about his decision.

He advised young medical students and doctors to know their passion which will give them a sense of purpose and a sense of direction.

“A career in research is not for everybody [just] as becoming a neurosurgeon is not for

everyone with a medical degree. Do not think first of the material gains. Think first if this field will provide you with satisfaction and a sense of fulfillment or if you enjoy doing it. Know your purpose in life and if this pur-pose is the one driving you, the result will be excellence in that particular field because you enjoy what you are doing, and subse-quently the material rewards will follow,” he said.


with SLE, compared to 20 percent among the healthy controls. In addition, 21 percent of the SLE patients suffered from depression, compared to 3 percent among the controls. No correlation was found between the severity of disease activity and incidence of psychologi-cal illness.

The second study, which was funded by the Lupus Inspired Advocacy or Rheuma-tology Educational Trust Foundation, Inc., is a descriptive study of the coping strate-gies employed by SLE patients and their caregivers. Group discussions and facili-tator-mediated surveys were held for 148 SLE patients and 69 caregivers to assess the psycho-emotional difficulties commonly en-countered. Coping strategies on the physi-

cal, psychological, emotional and social difficulties of having SLE were also elicited. The most common coping strategies reported in this study include support groups, prayers and family encouragement.

Both studies emphasized the importance of early detection of psychological problems among SLE patients and immediately insti-tuting interventions to allay such problems. Since SLE is a chronic illness, patients are at increased risk for psycho-emotional difficul-ties which impair their quality of life. Thus, a holistic approach to therapy is important to address not just the physical as[ects of the disease, but also the psycho-emotional burden faced by SLE patients and their caregivers.

Dr. Nicolo Cabrera

T he latest immunization recommenda-tions of the European League Against Rheumatism (EULAR) for patients

with autoimmune inflammatory rheumatic diseases (AIIRD) and the Centers for Dis-ease Control (CDC) Advisory Committee on Immunization Practices (ACIP) for immu-nocompromised patients are guides for the vaccination of patients with systemic lupus erythematosus (SLE), according to Dr. Maria Rhona Gatpandan-Bergantin of the Univer-sity of Santo Tomas Hospital and Faculty of Medicine and Surgery. She reminded the audience that infections

are still the leading cause of morbidity and mortality in SLE. Among the reasons she cit-ed were dysfunctions of complement system and mannose-binding lectin as well as innate and acquired immunity secondary to the disease itself. The use of immunosuppres-sive medications to treat the disease also in-creased the lupus patient’s risk for infection.

EULAR, CDC update lupus vaccination guidelines


She presented 12 recommendations issued by EULAR in 2010. Gatpandan-Bergantin explained, “There are a very, very limited number of trials or studies with regard to the effectiveness of vaccines in lupus, and mostly these are done on patients with quiescent disease,” empha-sizing that the patient’s SLE must be stable or inactive before administering any vaccines. While live-attenuated vaccines should generally be avoided in patients with SLE, the CDC ACIP recommendation issued last year made exceptions for measles-mumps-rubella (MMR) and varicella zoster vaccines provided that the patient was only mildly im-munosuppressed. According to CDC ACIP recommendations in 2012, immunocompromised patients with no previous vaccine should receive pneumo-coccal conjugate vaccine (PCV13) and then pneumococcal polysaccharide (PPSV23) af-ter at least eight weeks. If an immunocom-promised patient was previously vaccinated with PPSV23, he or she is given PCV13 one year after PPSV23. Conjugated vaccines, ex-

plained Gatpandan-Bergantin, recruited more memory cells. Subsequent doses of PPSV23 should be given no sooner than eight weeks af-ter PCV13 administration and at least five years since the most recent PPSV23 dose was administered. Based on the guidelines, Gatpandan-Bergantin advised for immunizations to be administered when the disease is stable. Although vaccines must be administered before starting B cell-depleting therapy, vaccinations may be done during use of disease-modifying anti-rheumatic drugs or tumor necrosis factor-alpha-blocking agents. Other recommended vaccines include hu-man papilloma virus vaccine for women until the age of 25 years; influenza, pneumococcal, Haemophilus influenzae b and meningococ-cal C vaccines for hyposplenic or asplenic patients with AIIRD; and hepatitis A or B vac-cinations for at-risk patients. Latest recom-mendations also advise against live-attenuat-ed vaccines as well as Bacille-Calmette Guérin vaccine.

End-organ damage seen in Filipino SLE patients

Dr. Yves Saint James Aquino

M ajority of systemic lupus erythema-tosus (SLE) patients have at least one

end-organ damage significantly associated with medications, according to a study done by Dr. Catherine Macapagal et al., under the Sections of Rheumatology in University of Santo Tomas Hospital and St. Luke’s Medical

Center. The study, which was funded by the Lu-pus Inspired Advocacy (LUISA) project of the Rheumatology Educational Trust Foundation, Inc., aimed to describe the prevalence of end-organ damage in a co-hort of adult SLE patients seen in the two tertiary hospitals. It included 187 patients (94.7 percent were females) who were seen


from January to June 2012 and were as-sessed using the Systemic Lupus Interna-tional Collaborating Clinics/SLE Damage Index (SLICC/SDI). Patients’ medical re-cords were reviewed for disease manifesta-tions, cumulative steroid dose and the use of immunosuppressive agents. As an autoimmune disease, SLE has been known to cause damage in several organs of the body. Some of these damages may not be immediately visible, with extent and sever-ity varying among patients. Results showed that 108 (57.7 percent) had at least one end-organ damage. Some of the more common manifestations included steroid-induced cataract (23 percent), pro-teinuria (20 percent) and stroke (13 percent). The study noted that damage occurred at an average of 6.6 years after diagnosis, with subsequent damage occurring at an average of 3 years after the preceding damage. Associated with the end-organ damage also included proteinuria (p=0.024), anemia

(p=0.028) and thrombocytopenia (p=0.049), which, according to the study, reflects a high disease activity that required increased doses of glucocorticosteroids. In terms of medications, the damage was associated with immunosuppressive treatment with cyclophosphamide (p=0.046) and cumula-tive prednisone dose of more than 10 grams (p=0.043). Prednisone, a corticosteroid medi-cation, is an anti-inflammatory that is used as treatment for kidney problems, arthritis, among others; while immunosuppressives such as cyclophosphamide are drugs that suppress the body’s immune response and are typically used in patients who failed to respond to corticosteroid therapy. Recent studies have pointed out that along with systemic autoimmunity, other factors such as end-organ responses and damages are important in disease outcomes. To avoid further complications, a regular work-up for signs of end-organ damage is needed in lupus patients.

Study reveals poorer outcomes in SLE with TB

Dr. James Salisi

F ilipinos with systemic lupus erythemato-sus (SLE) who have extrapulmonary tu-

berculosis (EPTB) and miliary pattern pulmo-nary TB (MPTB) had higher mortality rate and poorer outcomes than those with localized pulmonary TB alone, a study by Dr. Laniyata Hamijoyo and Dr. Sandra Navarra concluded. Researchers reviewed medical records of SLE patients in the University of Santo Tomas

Lupus Database from 1995 to 2011 in order to characterize their clinical course and compare variants of TB infection in terms of their out-comes. Their study revealed a high prevalence of TB among SLE patients in their database, revealing 108 patients with concomitant TB. The investigators grouped the patients into those with localized PTB and those with EPTB/MPTB. They compared the two groups in terms of demographic characteristics, SLE


Screening for CVD recommended for lupus patients

Dr. Nicolo Cabrera

Entry screening and timed evaluation for cardiovascular risk factors were recommend-ed by a team of investigators in a small study on the prevalence of cardiovascular risk fac-tors among patients with systemic lupus ery-thematosus (SLE) seen at the outpatient clinic of the Section of Rheumatology in the Philip-pine General Hospital from 2006 to 2011.

The team led by Dr. Aaron Joseph Tiu col-lected cross-sectional data from 50 adult pa-tients sufficiently documented in their charts to have met the American College of Rheu-matology Classification Criteria of 1982. All patients were female with a mean age of 29.1 years at diagnosis, commonly presenting with

photosensitivity and cutaneous manifesta-tions, hematologic manifestations or arthritis.

The study found that 38 percent (19 out of 50) had hypertension, 10 percent (five out of 50) had a history of smoking, 11.1 percent (two out of 18) were documented to be obese and 82.6 percent (19 out of 23) were documented to be dyslipidemic. Forty-eight percent of pa-tients with documented fasting blood sugar test results had no diabetes mellitus. Half of the patients had a documented electrocar-diogram result, while signs of left ventricular hypertrophy were seen in 4 percent and isch-emia in 8 percent.

Disease activity measured by the Mexican SLE disease activity index (Mex-SLEDAI) and duration and dosage of steroid therapy also

disease duration, prednisone dose and immu-nosuppressive use at the time of TB infection and outcome of TB infection. No significant differences were found be-tween the two groups’ demographic character-istics. Majority of the patients were female with an average age of 29 years old and an average of 45 months disease duration from SLE diag-nosis to TB diagnosis. However, patients with EPTB/MPTB tended to have longer disease duration from SLE diagnosis than those with localized PTB alone. The most common ETPB sites were arthritis and soft tissue abscesses. Patients with PTB alone had better out-comes than those with EPTB/MPTB. Analysis showed 85 percent of those with PTB alone re-

ported having complete resolution compared to just 65 percent of patients who had EPTB/MPTB. Moreover, no mortality was recorded for patients with localized PTB while 7 died in the other group. ETPB and MTB spread hematogenously, which is common in immunocompromised states. ETPB patients also have stronger ten-dency for TB recurrence than those with local-ized PTB alone. According to the researchers, infections are the leading cause of morbidity and mortal-ity in patients with SLE. TB infection is com-mon in developing countries and this study contributes in the understanding of SLE with TB in that context.


increased the risk for cardiovascular events and were termed non-traditional cardiovas-cular risk factors. The Mex-SLEDAI scores ranged from 0 to 23 and the mean was 3.9. All patients in the study were on steroid thera-py. It was prescribed for durations ranging from four to 168 months with a mean of 33.2 months. The mean duration prescribed pred-nisone with a dosage of >10 mg per day was 16.5 months while that for <10 mg per day was 12.7 months.

In terms of risk factor screening procedures, all patients had blood pressure measurements taken. A notable 36 percent had documented height and weight measurements, 48 percent had at least one fasting blood sugar result and 46 percent had at least one lipid profile result.

The study investigators admitted that the study population was small and screen-ing rates were low, but reported prevalence of these risk factors were generally compa-rable with previous local or international data.

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MARKET WATCH

With a strong history of advocating for public safety on skin health through informa-tion dissemination and consultation with competent and certified dermatologists, The

Philippine Dermatological Society, in partnership with Glenmark Philippines, Inc., launched the Imeptigo Awareness Campaign last October 25, 2012 in EDSA Shangri-La Hotel. The campaign aims to alleviate the burden of the disease and to prevent the increasing number of cases from year to year due to lacking accurate assessments of the disease, espe-cially in tropical developing countries like the Philippines. This initiative is designed to inform, treat and improve the quality of life of impetigo pa-tients. Awareness and support for prevention and treatment programs started last Novem-ber 2012 and will continue until March 2013.

PDS and GLENMARK fight impetigo

Representatives from PDS and Glenmark promote awareness


MARKET WATCH

T he Lupus Inspired Advocacy (LUISA), which promotes and protects the interest

of patients with systemic lupus erythematosus in the Philippines, and the Psoriatic Philippines launched the People Empowerment for Arthri-tis and Lupus (PEARL) through a musical and art exhibit entitled ‘The Patient, the Artist.” The event commenced with the opening of the art and photo exhibit, and then followed by a series of performances from lupus and arthri-tis patients. The program aimed to prove that even with debilitating illness, patients can still celebrate life through artistic expressions. With this exhibit, PEARL introduced pro-grams to help strengthen physicians and pa-tients through programs that include arthritis and lupus clinics, “Living Well” workshops, educational fora and fund-raising campaigns to assist the needs of challenged patients. For more information about the advocacy, visit www.luisaproject.org.

Arthritis and lupus patients empowered through art


MARKET WATCH

W ith the goal of proper cancer infor-mation dissemination, the Philippine

Society of Medical Oncology held a press conference to discuss facts and myths on cancer treatment that is being threatened by false claims of various herbal supplements. “Many of these herbal medicines, food and supplements are very attractive to can-cer patients due to their claimed quick re-sults and some for their low price tags,” said Dr. Oscar Gutierrez Jr., food and drug regulation officer IV of the Policy Planning Office of the Food and Drug Administra-tion (FDA). “[Supplements] have no approved ther-apeutic claims and no documented curative effects,” Gutierrez added. PSMO echoed similar sentiments and emphasized that patients should be given proper information. “The PSMO feels that it is imperative that we inform the pub-lic with documented facts regarding the use and misuse of herbal supplements to replace standard cancer treatment,” said PSMO president Dr. Felycette Gay Lapus. In her lecture, Lapus explained that un-like standard treatments, alternative thera-pies such as herbal supplements do not go through strict clinical trials. Dr. Ellie May Villegas, PSMO vice presi-dent and media committee chair, discussed

the difference of integrative oncology and alternative therapy. Integrative oncology involves evidence-based complementary therapies used along with standard treat-ments to control physical and emotional symptoms. These may include acupunc-ture, diet management, music therapy, meditation or yoga. “They are non-invasive, non-toxic and are adjunctive therapies. However, they are used with the standard-of-care treatment and not as the mainstream care,” said Vil-legas.The event was in line with the celebration of the Department of Health’s National Cancer Consciousness Week, and in partner-ship with pharmaceutical Companies Roche and Fresenius.

PSMO debunks myths on herbal supplements

Dr. Villegas, Dr. Lapus and Dr. Gutierrez during the press conference


MARKET WATCH

During a press conference last January 16, 2013, the Cardinal Santos Medical

Center (CSMC) recently opened its Hand Center with an exclusive robotic rehabili-tation technology to cater to patients in need of cures and procedures for all hand problems, from physical impairments in fingers to the upper extremities. The recently acquired technology, In-Motion, provides advanced rehabilita-tion for the hands, shoulders and arms for those afflicted with multiple sclerosis and other neurological conditions. It was developed through research in medical en-gineering at the Newman Laboratory for Biomechanics and Human Rehabilitation at the Massachusetts Institute of Technol-ogy. “We are proud to be the first to bring this kind of curative treatment in the Phil-ippines. Our expert staff is composed of highly rated physicians who went through specialized training in hand care here and abroad,” said Atty. Pilar Nenuca Almira, CEO of CSMC. InMotion facilitates motor learning by continually challenging the patient and encouraging active effort through precise and intensive exercises. The equipment

is interactive and able to respond to a pa-tient’s changing ability. The robotic arm, attached to a desktop and a computer, per-forms the four basic movements: passive, active assistive, active range of motion and progressive resistance. The hand Center works closely with Rehabilitation Medicine and is designed as a one-stop-shop for all hand ailments and treatments. For more information about the CSMC and the Hand Center, call (+632) 727 0001 or visit www.cardinalsantos. com.ph.

Cardinal Santos Medical Center introduces robotic rehab tech

Dr. Villegas, Dr. Lapus and Dr. Gutierrez during the press conference

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Conference Calender

FEBRUARY

Philippine Rheumatology Association 20th Annual MeetingFebruary 7-9, 2013Venue: Taal Vista Hotel, Tagaytay CityInfo: Philippine Rheumatology AssociationTelephone: (+632) 723 0101 loc. 5148Email: [email protected]: www.philippinerheumatology.org

19th Annual Convention, Pediatric Infectious Dis-ease Society of the PhilippinesFebruary 15-16, 2013Venue: Crowne Plaza, OrtigasInfo: Pediatric Infectious Disease Society of the PhilippinesTelephone: (+632) 374 1855Email: [email protected], [email protected]: www.pidsphil.org

6th ASEAN Rehabilitation Medicine Association Congress and 23rd Annual Convention, Philippine Academy of Rehabilitation MedicineFebruary 21-23, 2013Venue: Marriott Hotel, Manila Info: Philippine Academy of Rehabilitation Medicine, ASEAN Rehabilitation Medicine AssociationTelephone: (+632) 415 9048 or 410 1597 Email: [email protected]: www.eparm.org

2013 Philippine College of Radiology Annual Con-ventionFebruary 21-23, 2013Venue: SMX Convention Center, Pasay CityInfo: Philippine College of RadiologyTelephone: (+63) 373 8462Email: [email protected]: www.philippinecollegeofradiology.org

MARCH

11th Annual Convention, Philippine Society of Ultra-sound in Clinical MedicineMarch 15-16, 2013Venue: Hyatt Hotel and Casino, ManilaInfo: Philippine Society of Ultrasound in Clinical MedicineTelephone: (02) 400 9483Email: [email protected] Website: www.psucmi.org

5th Regional Conference, Philippine Society for Pediatric Gastroenterology, Hepatology, and NutritionMarch 6, 2013Venue: Baguio Country Club, Baguio CityInfo: Philippine Society for Pediatric Gastroenterology, Hepatology, and NutritionTelephone: (+632) 355 7499Email: [email protected]: www.pspghan.org

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26 February 2013 News

Ticagrelor recommended for STEMI in latest ACC/AHA guidelines

Rajesh Kumar

The American College of Cardiology (ACC) and the American Heart Associ-ation (AHA) have updated their clini-

cal practice guidelines for the management of ST-elevation myocardial infarction (STEMI) to include a class I recommendation for the use oral antiplatelet medicine ticagrelor (Bril-inta®, AstraZeneca).

The guidelines recommend that reperfu-sion therapy be given in a timely manner to all eligible patients with STEMI undergoing either percutaneous coronary intervention (PCI) or fibrinolytic therapy. [J Am Coll Cardiol 2012; doi:10.1016/j.jacc.2012.11.019] They also suggest that patients who present to a non-PCI-capable hospital should be considered for transfer either for primary PCI, or if an-ticipated time to PCI is greater than 2 hours, after fibrinolysis.

Appropriate antithrombotic therapy, in-cluding dual antiplatelet and anticoagulant therapy (with clopidogrel, prasugrel or ti-cagrelor), should be used during and after re-perfusion therapy, a report on the guideline revisions added.

The recommendation on “Antiplatelet Therapy to Support Primary PCI for STEMI” (4.4.1) suggested that aspirin at a dose of 162 to 325 mg should be given before primary PCI

and should be continued indefinitely thereaf-ter; while a loading dose of a P2Y12 receptor inhibitor such as clopidogrel 600 mg, prasug-rel 60 mg or ticagrelor 180 mg should be given as early as possible or at the time of primary PCI.

Thereafter, maintenance doses of clopi-dogrel 75 mg daily, prasugrel 10 mg daily or ticagrelor 90 mg twice-a-day should be given for 1 year to those receiving a bare metal or drug-eluting stent during primary PCI.

27 February 2013 News

The Thrombus Receptor Antagonist in Sec-ondary Prevention of Atherothrombotic

Ischaemic Events (TRA 2° P) – TIMI 50 trial reported in April 2012 showed that treatment with vorapaxar, a selective antagonist of pro-tease-activated receptor 1, for patients with previous myocardial infarction (MI), ischemic stroke or peripheral arterial disease, reduced the risk of cardiovascular death, MI or stroke by 13 percent, but increased the risk of bleed-ing. Now a subgroup analysis from that trial has concentrated on patients with prior MI. [Lancet 2012;380:1317–1324]

In this subgroup, a total of 17,779 patients had experienced an MI 2 weeks to 12 months previously. Randomization was to vorapaxar

2.5 mg daily or placebo in addition to aspirin, and average follow-up was 2.5 years. Cardio-vascular death, MI or stroke occurred in 610 vorapaxar recipients vs 750 patients receiving placebo, giving estimated 3-year rates of 8.1 vs 9.7 percent, a significant 20 percent reduction with vorapaxar. The estimated 3-year rates of moderate or severe bleeding were 3.4 vs 2.1 percent, a significant 61 percent increase with vorapaxar. There was a nonsignificant increase in intracranial hemorrhage with vorapaxar.

The researchers concluded that vorapax-ar reduced the risk of cardiovascular death, repeat MI and stroke in post-MI patients, but increased the risk of moderate or severe bleeding.

Vorapaxar after myocardial infarction

Metalloacid coating the newest weapon against nosocomial infections

Pank Jit Sin

A surface-coating of metalloacids could help in the war against nosocomial in-fections and antimicrobial resistance,

reports a new study. The study, published in Antimicrobial Resis-

tance Infection Control, showed a surface coat of molybdenum trioxide metalloacid could effectively kill microbial strains, including multidrug-resistant strains. The findings, by researchers from Centre Hospitalier Univer-sitaire de Tours and the Centre Hospitalier Universitaire de Besançon, France, are a result of experimentation of biocidal activity of sur-

Metalloacids may help hospitals in the fight against antimicrobial resistance.

28 February 2013 Newsfaces coated with molybdenum metalloacid. [In Press]

The researchers exposed two different sur-faces – one metalloacid coated and the other being non-coated – to 11 pathogenic bacteria commonly associated with nosocomial in-fections, including two Staphylococcus aureus strains; Clostridium difficile; three extended-spectrum beta-lactamase-(ESBL)-producing Enterobacteriaceae strains; vancomycin-resis-tant Enterococcus faecium; Pseudomonas aerugi-nosa; multidrug-resistant Acinetobacter bauman-nii; two fungal strains of Candida albicans and Aspergillus fumigatus.

It was found that the surfaces coated with metalloacid could significantly inhibit all non-spore-forming organisms within 2 to 6 hours of contact. In comparison, uncoated surfaces still exhibited substantial amounts of micro-organisms when tested after the same time.

However, they also found that spore-form-ing organisms were totally unaffected by the metalloacid coating.

The researchers suggested that biocidal reaction is caused by the diffusion of hy-droxonium ions (H3O+) through microbe cell membranes, which alters the cells’ enzyme transport systems and inhibits metabolic activity.

According to lead author Nathalie van der Mee-Marquet, the findings could help hospitals in the fight against antimicrobial resistance as there is less likelihood that sus-ceptible microbes will develop resistance to-wards the metalloacid coating.

She suggested that further studies be car-ried out to determine if coating metalloacids on medical devices will prove to be a suc-cessful step in the prevention of nosocomial infections.

High troponin levels linked to poorer prognosis in chronic heart failureRajesh Kumar

Elevated cardiac troponin levels in patients with chronic but stable heart failure is

linked to higher mortality risk and adverse cardiovascular outcomes, according to a sys-tematic review.

The role of cardiac troponin in diagnosing myocardial infarction is already well estab-lished. Its elevated levels are seen in many other cardiac and non-cardiac conditions in-cluding acute pulmonary embolism, myocar-ditis and renal failure. Higher troponin levels also act as markers for a poor prognosis of

Circulating troponin levels appear to be correlated to heart failure disease severity.

29 February 2013 Newsthese conditions.

In this instance, the researchers tried to establish its prognostic value in chronic sta-ble heart failure [Heart 2012; DOI:10.1136/heartjnl-2012-301779]. They analyzed patient data from 16 clinical trials to extract the prog-nostic value of baseline cardiac troponin ele-vation in these patients and found that it was associated with a high risk of mortality (haz-ard ratio [HR], 2.85).

Although high-sensitivity assays detected cardiac troponin in a higher proportion of pa-tients compared with low-sensitivity assays, there was no statistically significant difference between the two groups [p=0.54].

“Our analysis confirmed the prognostic val-ue of troponin assays and highlights the pres-ence of circulating troponins in stable patients with chronic heart failure as markers of un-derlying myocardial necrosis. [This indicates]

disease severity, regardless of troponin type or sensitivity,” said co-researcher Dr. W.H. Wil-son Tang, cardiologist at the Heart and Vas-cular Institute, Cleveland Clinic in Cleveland, Ohio, US.

“Further studies in this area are warranted, particularly regarding therapeutic responses to detectable troponin levels,” concluded Tang.

The cause of cardiac troponin release in patients with chronic heart failure is unclear. The basic concept behind this is irreversible cardiomyocyte damage, although the poten-tial for reversible damage as a cause of cardiac troponin is under debate, said researchers.

Demand–supply mismatch of oxygen at cellular level may be a cause of troponin release, which could explain the reason for cardiac troponin elevation in septic shock, se-vere hypotension and tachyarrhythmias, they said.

Radha Chitale

New research describing the mucus-caus-ing pathway activated in many respi-

ratory diseases led researchers to develop a series of drugs to inhibit excess mucus pro-duction and potentially limit death from these conditions.

“[Excess mucus secretion] is an invariable feature of acute respiratory illness and a char-acteristic feature of chronic lung diseases, such as asthma and chronic obstructive pul-monary disease (COPD),” said Dr. Michael J. Holtzman, professor of medicine at Washing-

New mucus-inhibiting therapies may help patients with asthma, COPD

Lab research points to the potential benefits of therapeutics which inhibit excess mucous production.

30 February 2013 Newston University School of Medicine in St. Lou-is, Missouri, US. “It’s a huge unmet medical problem and is only increasing… throughout the world.”

Stimulants such as allergens, viruses and cigarette smoking activate a pathway that results in extra mucus production, meant to catch small particles and infectious bacteria and keep them from penetrating into respira-tory pathways.

Two key players in this pathway are the CLCA1 gene that activates an eponymous protein in response to environmental stimuli. This protein, with help from an enzyme called MAPK13, enables mucus production. [J Clin Invest 2012; doi:10.1172/JCI64896]

Holtzman noted the existence of inhibitors for MAPK14, which is similar to MAPK13.

“These drugs bind to a specific pocket in MAPK14 to block its activity,” he said.

Modifying these therapeutic molecules to make them smaller and a better fit for the in-hibiting pockets of MAPK13 resulted in a 100-fold reduction in mucus production in human airway cell cultures.

“These properties should translate into

more sustained and potent effects for use as tool compounds and for further drug devel-opment,” the researchers said. “Additional work will have to be done to fully character-ize the… specificity of the present compounds and perhaps to develop others with greater specificity.”

Importantly, the study was carried out in human cells rather than in a mouse model be-cause of divergent mucus secretion pathways.

Currently, there are few effective treat-ments for excess mucus, despite mucus over-production likely being responsible for much of the morbidity and mortality associated with respiratory conditions, the researchers noted.

New MAPK13 inhibitor therapies could impact other conditions in which excess mu-cus represents respiratory problems, includ-ing cystic fibrosis and the common cold.

Having characterized the dominant mucus-causing pathway in people with respiratory diseases, the researchers said “the [study] re-sults validated a novel therapeutic approach to hypersecretory diseases of the pulmonary airways and perhaps other sites as well.”

31 February 2013 Drug Prof i le

Ticagrelor: Latest recommendations under-line antiplatelet agent’s usefulness in ACSOral antiplatelet agent ticagrelor (Brilinta®, AstraZeneca) was recently given a class I recommendation in the latest revision of the American College of Cardiology (ACC) and American Heart Association (AHA) clinical practice guidelines for the management of patients with ST-elevation myocardial infarction (STEMI). The following article discusses the management of STEMI and other acute coronary syndromes (ACS), profiling the drug ticagrelor.

Naomi Adam, MSc (Med), Category 1 Accredited Education Provider (Royal Australian College of General Practitioners)

Antiplatelet agents for the management of ACS

Cardiovascular diseases remain the lead-ing cause of mortality worldwide and more than half of these deaths involve coronary ar-tery disease with acute coronary syndromes (ACS). Variants include ACS with and with-out ST-segment elevation, such as unstable an-gina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial in-farction (STEMI). [Postgrad Med J 2012;88:391-396]

The pathophysiology of all of these syn-dromes features the disruption of an athero-sclerotic plaque that results in intracoronary thrombogenesis. Platelets play a key role in both the development of atherosclerosis and subsequent thrombosis. In acute thrombosis there is a multiple-step mechanism that in-volves platelet adhesion, activation and ag-gregation at the site of injury, followed by cross-linking through fibrin, ultimately lead-ing to obstruction of the coronary vessel. Hence medications that inhibit platelet action

are a mainstay of therapy in this setting. [Curr Cardiol Rep 2012;14:457-467]

Aspirin has been the cornerstone of ACS treatment for decades. Its action is mostly due to inactivation of platelet cyclooxygenase 1, which leads to the inhibition of thromboxane generation, and thus disrupts platelet aggre-gation. However, aspirin alone fails to pre-vent the majority of recurrent events and this has prompted investigations into alternative methods of blocking platelet action. [Postgrad Med J 2012;88:391-396]

At a molecular level, one of the critical com-ponents for platelet aggregation is the platelet P2Y12 receptor. Therefore, blockade of the P2Y12 receptor is an important treatment strategy that is employed in conjunction with aspirin. The clinical benefits of dual antiplate-let treatment with aspirin plus clopidogrel in

32 February 2013 Drug Prof i lethe management of ACS are well established. However, clopidogrel is a pro-drug that re-quires hepatic activation and there are several concerns regarding its use. These include de-layed onset of action, variability in antiplatelet effects, prolonged recovery of platelet func-tion after discontinuation and interactions with commonly used agents such as proton pump inhibitors. While the use of clopidogrel has been a beneficial advance in the treatment of ACS, its shortcomings have prompted in-vestigations of alternative P2Y12 receptor antagonists. [Postgrad Med J 2012;88:391-396, Curr Cardiol Rep 2012;14:457-467]

TicagrelorTicagrelor is the first member of a new

class of antiplatelet agents – the cyclopentyl-triazolopyrimidines – to undergo clinical de-velopment. Its inhibitory effects on platelet function are mediated predominantly via the P2Y12 receptor, however, ticagrelor provides more effective inhibition of platelet function, with a faster onset and offset of action than clopidogrel. [Drugs 2011;71:909-933]

Pharmacokinetics and metabolismFollowing oral administration, ticagrelor is

rapidly absorbed and converted to its major metabolite – AR-C124910XX. Unlike clopido-grel, ticagrelor is itself an antagonist of the P2Y12 receptor. The pharmacokinetics of ti-cagrelor are linear with dose-proportional ex-posure up to doses of 1,260 mg. Peak plasma concentrations are reached at a median of 1.5 hours of administration and it has a mean half-life of 7 hours. The timing of a meal relative to a dose of ticagrelor has no appre-ciable effect up its pharmacokinetics. [Drugs 2011;71:909-933]

Metabolism of ticagrelor occurs predomi-

nantly via CYP3A4 and CYP3A5. Elimination of ticagrelor and AR-C124910XX occurs pri-marily via hepatic metabolism and biliary se-cretion, respectively. [Drugs 2011;71:909-933]

Clinical efficacyThe pivotal clinical trial of ticagrelor was

the Platelet Inhibition and Patient Outcomes (PLATO) study. This was a multicenter, dou-ble-blind, randomized trial that compared P2Y12 antagonists for the prevention of car-diovascular events on a background of as-pirin therapy in 18,624 patients hospitalised with an ACS. Subjects were assigned to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300–600 mg loading dose, 75 mg daily thereafter). The primary efficacy endpoint was the time to the first occurrence of composite of death from vascular causes, myocardial infarction, or stroke. After 12 months of follow up, the primary endpoint occurred significantly less often in in the ticagrelor group than in the clopidogrel group (in 9.8 percent of patients vs 11.7 percent; hazard ratio, 0.84; 95% CI 0.77–0.92; p<0.001). There was no difference in the overall major bleeding rate between the two groups, though ticagrelor was associated with a significant increase in the rate of non-procedure-related bleeding. [N Engl J Med 2009;361:1045-1057]

Adverse effectsIn clinical trials, adverse events associated

with ticagrelor included ventricular pauses, dyspnea, hyperuricemia, and increased creat-inine. [Drugs 2011;71:909-933] Contraindica-tions according to the product label are active pathological bleeding, a history of intracranial hemorrhage and moderate-to-severe hepatic impairment. The label also states that ticagre-

33 February 2013 Drug Prof i lelor should be used with caution in patients at risk of bleeding (eg, recent trauma, surgery, GI bleeding, concomitant NSAIDs or fibrino-lytics). If a patient reports new, prolonged or worsened dyspnea, this should be investigat-ed fully and if not tolerated, treatment with ticagrelor should be stopped. [Brilinta Product Monograph. February 2012]

There is a potential for drug interactions mediated by CYP3A4, hence co-administra-tion with strong inhibitors such as ketocon-azole, clarithromycin, nefazodone, ritonavir and atazanavir is contraindicated. [Drugs 2011;71:909-933, Brilinta Product Monograph. February 2012]

DosingThe approved dosage is as per that used in

the PLATO trial: treatment should be initiated with a loading dose of 180 mg ticagrelor (two tablets of 90 mg) and then continued at 90 mg twice a day for up to 12 months. Patients taking ticagrelor should also take low-dose aspirin daily, unless specifically contraindicated. Fol-lowing an initial loading dose of aspirin, the maintenance dose is 75–150 mg per day.

Guideline recommendations for ticagrelor The UK National Institute for Clinical Ex-

cellence has recommended that ticagrelor in combination with low-dose aspirin is recom-mended for up to 12 months as a treatment option in adults ACS, including those with:

• ST-segment-elevation myocardial infarc-tion (STEMI) – defined as ST elevation or new left bundle branch block on electrocardio-

gram – that cardiologists intend to treat with primary percutaneous coronary intervention (PCI)

• non-ST-segment-elevation myocardial infarction (NSTEMI) or admitted to hospi-tal with unstable angina – defined as ST or T wave changes on electrocardiogram sugges-tive of ischemia.

The NICE recommendations further sug-gest that before ticagrelor is continued be-yond the initial treatment, the diagnosis of unstable angina should first be confirmed, ideally by a cardiologist. [NICE technology ap-praisal guidance 236. www.nice.org.uk/ta236. October 2011]

Subsequently, the American Heart Associa-tion (AHA) Task Force on Practice Guidelines and the American College of Cardiology Foun-dation (ACCF) have also updated their rec-ommendation to state that ticagrelor should be considered as an equal option to clopido-grel for patients with NSTEMI [Circulation 2012; 126: 875–910] and for STEMI [J Am Coll Cardiol 2012; doi:10.1016/j.jacc.2012.11.019].

Further long-term and comparative effi-cacy and tolerability data will be needed to definitively position ticagrelor with respect to other antiplatelet agents. However, the data so far indicate that ticagrelor is a promising option for the treatment of patients with ACS and may be of particular use in those at high risk of ischemic events or unresponsive to clopidogrel.

Author disclosures: None

34 February 2013 Research Reviews

New drug promising in HF with preserved LVEF

About half of patients with heart failure (HF) have preserved left ventricular ejection frac-tion (LVEF). Such HF is difficult to treat and the pathophysiology has yet to be completely

understood. There may be abnormal diastolic function, increased vascular stiffness or subtle abnormalities of systolic function. LCZ696 is an angiotensin receptor neprilysin inhibitor, a new class of drug that combines a neprilysin (neutral endopeptidase 24.11) inhibitor prodrug and the angiotensin receptor blocker valsartan, in one compound.

A multinational trial at 65 centers in 13 countries has shown that LCZ696 reduces levels of NT-proBNP (a marker of left ventricular wall stress) to a greater extent than valsartan in patients with HF with preserved LVEF.

The study included a total of 301 patients with New York Heart Association class II and III HF, LVEF at least 45 percent and an NT-proBNP level >400 pg/ml. Randomization was to LCZ696 or valsartan for 36 weeks. In the LCZ696 group the mean NT-proBNP level was 783 pg/ml at baseline and 605 pg/ml at 12 weeks; in the valsartan group the correspond-ing levels were 862 and 835 pg/ml, a significantly better response with LCZ696. Adverse events were similar in the two groups and the rate of serious adverse events was 15 percent (LCZ696) vs 20 percent (valsartan).

LCZ696 was superior to valsartan using this endpoint. Further investigation is needed.

Solomon SD et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised

controlled trial. Lancet 2012; 380: 1387–95; Cleland JGF, Clark AL. Heart failure – does it matter whether LVEF is reduced? Ibid: 1363–5 (comment).


Zotarolimus-eluting vs sirolimus-eluting stentsIt has been postulated that drug-eluting stents may promote late stent thrombosis by sup-

pressing neointimal hypoplasia and inhibiting vessel healing. The Patient Related OuT-comes with Endeavor versus Cypher stenting Trial (PROTECT) has compared a low potency drug eluting stent (the Endeavor zotarolimus-eluting stent, E-ZES) with a higher potency stent (the Cypher sirolimus-eluting stent, C-SES).

A total of 8,791 patients were randomized at 196 centers in 36 countries to E-ZES or C-SES, and 8,709 were included in the analysis. The rates of definite or probable stent thrombosis at 3 years were 1.4 percent (E-ZES) vs 1.8 percent (C-SES), a nonsignificant difference. The rate of use of dual antiplatelet therapy was 96 percent at hospital discharge, 88 percent at 1 year, 37 percent at 2 years, and 30 percent at 3 years.

There was no evidence that the lower potency stent was significantly superior at 3 years. A difference may emerge over a longer period of time. Both of these devices have been super-seded by newer devices.

Camenzind E et al. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet 2012; 380: 1396–405; Byrne RA et al. The battle against stent thrombosis – to protect and to serve. Ibid: 1365–7 (comment).

Diclofenac and anastomotic leakage after colorectal resectionThere is evidence from retrospective studies that the use of nonsteroidal anti-inflammatory

drugs (NSAIDs) after colorectal resection may increase the risk of anastomotic leakage. A prospective cohort study in Denmark has confirmed a link between diclofenac treatment and anastomotic leakage.

The study included 2,756 patients (52 percent men) who had colonic or rectal resection with primary anastomosis for cancer at six specialized Danish centers. Postoperative NSAID treatment had been received by 32 percent of these patients. Patients who received diclof-enac or ibuprofen postoperatively were significantly more likely to need reoperation for anastomotic leakage compared with patients who had not been given NSAIDS (12.8 percent vs 8.2 percent). Before adjustment, the increased risk was 7.8 pecent with diclofenac and 3.2 percent with ibuprofen. After statistical adjustment for other risk factors, only diclofenac was significantly associated with increased risk (a 7.2-fold increase).

Use of diclofenac (for at least 2 days in the 7 days after operation) was associated with a significant increase in risk of anastomotic leakage needing reoperation.

Klein M et al. Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: cohort study based on prospective data. BMJ 2012; 345 (Oct 20): 19 (e6166).


Resistance to second-line drugs in MDR tuberculosis

The emergence of extensively drug-resistant (XDR) tuberculosis and its

increasing prevalence are consequences of the increased use of second-line drugs for multidrug-resistant (MDR) tubercu-losis. A study in eight countries (Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand) has il-lustrated the problem.

The study included 1,278 consecutive adults with MDR tuberculosis during the years 2005 to 2008. Overall, 43.7 per-cent of these patients showed resistance to at least one second-line drug, 20.0 percent to at least one injectable second-line drug, and 12.9 percent to at least one fluoroquinolone. The prevalence of XDR tuberculosis was 6.7 percent (varying from 0.8 percent in the Philip-pines to 15.2 percent in South Korea). The strongest risk factor for resistance to second-line drugs was previous treatment with these drugs and this increased the risk of XDR tuberculosis more than fourfold. Resistance to second-line drugs was also associated with unemployment, alcohol abuse and smoking. Fluoroquinolone resistance and XDR tu-berculosis were more prevalent among women than among men.

Previous treatment with second-line drugs is the strongest risk factor for resistance to these drugs and XDR tuberculosis. Policies for laboratory capacity and diagnostic strategies could be guided by representative drug-susceptibility information in each country.

Dalton T et al. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a

prospective cohort study. Lancet 2012; 380: 1406–17; Hoffner S. Unexpected high levels of multidrug-resistant tuberculosis present new challenges for

tuberculosis control. Ibid: 1367–9 (comment).


Opiate substitution reduces HIV risk

Opiate substitution treatment is used for addiction to heroin or other opi-

oids and associated reductions in injecting risk behavior may reduce the risk of HIV infection. A systematic review and meta-analysis has confirmed this protection.

The review included 12 published and three unpublished studies of methadone maintenance treatment with over 26,738 person-years of follow-up and 1,016 new HIV infections. A meta-analysis of nine studies showed that opiate substitution treatment was associated with a significant 54 percent reduction in HIV risk among people who inject drugs. There was a sug-gestion that the risk reduction might in-crease with duration of opiate substitution treatment. Geographical region, the provi-sion of incentives, site of recruitment, and the proportion of subjects who were wom-en or from ethnic minorities did not affect the findings.

Opiate substitution therapy significantly reduces the risk of HIV infection among people who inject drugs.

MacArthur GJ et al. Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ 2012; 345

(Oct 20): 16 (e5945); Gowing LR. The role of opioid substitution treatment in reducing HIV transmission. Ibid: 10 (e6425) (editorial).


Paroxysmal AF: radiofrequency ablation vs drug therapy as first treatment

European researchers have compared radiofrequency catheter ablation with antiarrhyth-mic drug therapy as first treatment for paroxysmal atrial fibrillation (AF).

A total of 294 patients aged <70 years with paroxysmal AF and no previous drug therapy were randomized to radio frequency catheter ablation or treatment with class Ic or III antiar-rhythmic drugs (flecainide, propafenone, or, if class Ic agents contraindicated, amiodarone or sotalol). At follow-up, 7-day Holter-monitoring recordings were obtained at 3, 6, 12, 18, and 24 months. The burden of AF was taken to be the proportion of time in AF in Holter monitoring.

Neither the cumulative burden of AF (90th percentile, 13 percent in the ablation group and 19 percent in the drug group) nor the burden at 3, 6, 12, or 18 months was significantly dif-ferent between the two groups. At 24 months the burden was significantly less in the ablation group (90th percentile, 9 percent vs 18 percent) and the rates of freedom from any AF (85 percent vs 71 percent) and freedom from symptomatic AF (93 percent vs 84 percent) were significantly higher in the ablation group. There were three cases of cardiac tamponade and one death from a procedure-related stroke in the ablation group. Over a third (36 percent) of patients in the drug therapy group had supplementary ablation.

These researchers conclude that over 2 years there was no significant difference between the two treatment strategies in the cumulative burden of AF. Editorialists suggest that patient and doctor should reach a consensus after full discussion taking into account the patient’s preference.

Cosedis Nielsen J et al. Radio frequency ablation as initial therapy in paroxysmal atrial fibrillation. NEJM 2012; 367: 1587-95; Stevenson WG; Albert CM.

Catheter ablation for paroxysmal atrial fibrillation. Ibid: 1648–9 (editorial).


Cardiac arrest in hospital: How long should resuscitation efforts continue?

How long attempts to resuscitate patients after cardiac arrest should continue is uncertain. A study at 435 US hospitals has provided useful information.

Between 2000 and 2008, there were 64,339 patients with cardiac arrest at the 435 hospitals; 31,198 patients (48.5 percent) had return of spontaneous circulation after resuscitation and 9,912 (15.4 percent) survived to hospital discharge. Among non-survivors, the median du-ration of resuscitation was 20 minutes. Return of spontaneous circulation and survival to hospital discharge were each 12 percent more likely in hospitals in which average resuscita-tion time for non-survivors was longer (25 minutes) compared with those in which it was shorter (16 minutes).

Hospitals in which resuscitation attempts were longer in non-survivors had better rates of return of circulation and survival.

Goldberger ZD et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet 2012; 380: 1473–81;

Nolan JP, Soar J. Duration of in-hospital resuscitation: when to call time: Ibid: 1451–3 (comment).


Job strain and coronary disease

There is evidence that job strain (high job demands and low job control)

may increase the risk of coronary disease. Present evidence, however, is possibly subject to publication bias and there may be an element of reverse causation. Now a meta-analysis of published and unpub-lished studies has suggested a small but significant effect of job strain.

The meta-analysis included individual participant data from 13 European co-hort studies (197,473 participants with no coronary disease at baseline from 1985 to 2006). Job strain was measured by ques-tionnaire. Incident coronary disease was defined as coronary death or first nonfatal myocardial infarction. Job strain was re-ported by 15 percent of participants. Over a mean follow-up of 7.5 years, there were 2,358 incident coronary disease events. After adjustment for age and sex, job strain was associated with a significant 23 percent increase in risk of incident coro-nary disease (43 percent in published studies, 16 percent in unpublished). After exclusion of coronary events occurring within 5 years of baseline, the increase associated with job strain was 30 percent. The association of coronary disease with job strain remained significant after adjusting for multiple confounding factors. The population attributable risk was 3.4 percent.

It is concluded that job strain increases coronary risk but the effect is small compared with standard risk factors such as smoking.

Kivimäki M et al. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet 2012; 380:

1491–7; Netterstrøm B. Job strain as a measure of exposure to psychological strain. Ibid: 1455–6 (comment).


Self-harm and premature death

People who self-harm are at increased risk of death from suicide, accidents, and natural causes. Both self-harm and suicide are associated with low socioeconomic status. Now

a study based on emergency departments in three English cities (Oxford, Manchester and Derby) has shown that people who self-harm often have physical as well as psychological problems and their life expectancy is compromised.

The study included 30,950 people who presented to the three emergency departments with self-harm (self-poisoning or self-injury) in the years 2000 to 2007. The average follow-up was for 6 years and overall mortality during follow-up was 6.1 percent. The standardized mortal-ity rate was 3.6 (4.1 for males and 3.2 for females). Deaths from natural causes were up to 7.5 times more frequent than expected. All-cause deaths meant 31 years of life lost (YLL) for both males and females who self-harmed. For deaths from natural causes the YLL was around 26 years, and for deaths from external causes 40 years. Circulatory system deaths accounted for 13 percent of deaths and digestive system deaths for 12 percent of male deaths and 18 percent of female deaths. All-cause mortality was strongly related to socioeconomic deprivation in both sexes. Socioeconomic deprivation was associated with an increased risk of death from natural causes but not from external causes.

Self-harm is associated with both physical and mental health problems and with many years of life lost.

Bergen H et al. Premature death after self-harm: a multicentre cohort study. Lancet 2012; 380: 1568–74; Caine ED. Self-harm behaviour: rethinking

physical and mental health. Ibid: 1536–8 (comment).


Dengue vaccine in Thailand

It is thought that about half of the global population are at risk of contracting dengue.

There is no specific treatment and no vaccine. Now a recombinant, live, attenuated tetrava-lent dengue vaccine (CYD-TDV) has been as-sessed in Thailand.

A total of 4,002 schoolchildren aged 4–11 years were randomized (2:1) to dengue vac-cine or control (rabies vaccine or placebo) with three doses at 6-month intervals, and followed up for 25 months. The vaccine efficacy against virologically confirmed symptomatic dengue occurring at least 12 months after the third dose was 30.2 percent. This low overall efficacy was explained by a very low (not significantly different from zero) efficacy against serotype 2 virus, which caused 59 percent of the dengue episodes. Efficacy against serotypes 1, 3 and 4 was 61 percent, 82 percent and 90 percent, re-spectively. The vaccine was well tolerated.

The vaccine is safe and effective against three of four serotypes. Further studies are planned.

Sabchareon A et al. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled

phase 2b trial. Lancet 2012; 380: 1559–67; Halstead SB. Dengue vaccine development: a 75% solution? Ibid: 1535–6 (comment).

Benzodiazepines and dementia risk

Case-control and cohort studies have shown that benzodiazepines may affect cognition. A study in France has shown that benzodiazepine use is associated with an increased risk

of dementia.The PAQUID study was a 20-year follow-up study of a cohort of 3,777 unselected people

aged 65 or over in southwest France. An analysis of a main cohort of 95 new users of benzo-diazepines and 968 non-users (mean age, 78 years) showed a significant increase in risk of dementia of 62 percent associated with new use. Pooled analysis of five cohorts showed a significant 43 percent increase in risk. A nested case-control analysis including 467 patients with dementia and 1,810 controls showed a 55 percent increase in risk with ever-use com-pared with never-use. The risk was increased significantly only in past users (at least 5 years previously) and not in recent users. Adjustment for factors associated with benzodiazepine use and for factors possibly predictive of dementia did not alter the findings.

Benzodiazepine use in the past is associated with increased risk of dementia.

Billioti de Gage S et al. Benzodiazepine use and risk of dementia: population-based study. BMJ 2012; 345 (Oct 27): 14 (e6231).

43 February 2013 CalendarFebruaryFood Allergy and Anaphylaxis Meeting (FAAM) 20137/2/2013 to 9/2/2013Location: Nice, FranceInfo: EAACI FAAM 2013 SecretariatTel: (33) 1 7039 3554Fax: (33) 1 5385 8283Email: [email protected] Website: www.eaaci-faam.org/

International Meeting on Emerging Diseases and Surveillance (IMED 2013)15/2/2013 to 18/2/2013Location: Vienna, AustriaInfo: International Society for Infectious DiseasesTel: (617) 277 0551Fax: (617) 278 9113 Email: [email protected]: www.isid.org/imed/Index.shtml

Asian Pacific Society of Cardiology 2013 Congress21/2/2013 to 24/2/2013Location: Pattaya, ThailandInfo: Kenes Asia (Thailand Office)Tel: (66) 2 748-7881Fax: (66) 2 748-7880Email: [email protected]: www2.kenes.com/apsc2013/pages/home.aspx

International Conference on Functional Biomedical Imaging 23/2/2013 to 24/2/2013 Location: Ho Chi Minh City, Vietnam Info: SCIEI Tel: (1) 6177166164Email: [email protected] Website: www.icfbi.org

March23rd Annual Meeting of the Society for Virology 6/3/2013 to 9/3/2013Location: Kiel, Germany Info: Conventus Congress Management & Marketing GmbHTel: (49) 3641 311 61 60Fax: (49) 3641 311 62 43Email: [email protected] Website: www.virology-meeting.de

3rd Emirates Hematology Conference 7/3/2013 to 9/3/2013 Location: Dubai, UAE Info: Emirates Society of Haematology Tel: (971) 4 4270492 Fax: (971) 4 4270493Email: [email protected] Website: www.ehc2013.com

62nd American College of Cardiology (ACC) Annual Scientific Session9/3/2013 to 11/3/2013Location: San Francisco, California, USInfo: American College of Cardiology FoundationTel: (1) 415 800 699 5113Email: [email protected]: www.accscientificsession.org/Pages/home.aspx

28th Annual European Association of Urology Congress15/3/2013 to 19/3/2013Location: Milan, ItalyInfo: European Association of UrologyTel: (39) 2 4342 6275Fax: (39) 2 4801 0270Email: [email protected]: www.eaumilan2013.org

65th American Academy of Neurology Annual Meeting 16/3/2013 to 23/3/2013 Location: San Diego, California, US Info: American Academy of Neurology Tel: (1) 612 928 6000Fax: (1) 612 454 2746 Email: [email protected] Website: www.aan.com

4th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association27/3/2013 to 30/3/2013Location: Shanghai, ChinaInfo: Asian Pacific Hepato-Pancreato-Biliary AssociationTel: (86) 21 350 30066Fax: (86) 21 655 62400Email: [email protected]: www.aphpba2013shanghai.org

44 February 2013 CalendarUPCOMINGEuropean Congress on Osteoporosis and Osteoarthritis17/4/2013 to 20/4/2013 Location: Rome, Italy Info: International Osteoporosis Foundation Tel: (32) 4 254 1225 Email: [email protected]: www.ecceo13-iof.org

48th European Association for the Study of the Liver 24/4/2013 to 28/4/2013 Location: Amsterdam, Netherlands Info: European Association for the Study of the LiverTel: (31) 20 549 1212 Fax: (31) 20 646 4469Email: [email protected]: www.easl.eu/_the-International-liver-congress/general-information

5th Association of Southeast Asian Pain Societies Conference28/4/2013 to 5/5/2013Location: SingaporeInfo: Pain Association of SingaporeTel: (65) 6292 4710Fax: (65) 6292 4721Email: [email protected] Website: www.aseaps2013.org

American Urology Association (AUA) Annual Meeting4/5/2013 to 8/5/2013Location: San Diego, California, USInfo: AUATel: (1) 410 689 3700Fax: (1) 410 689 3800Email: [email protected] Website: www.aua2013.org

World Congress of Nephrology31/5/2013 to 4/6/2013Location: Hong KongInfo: ISN World Congress of Nephrology 2013Tel: (852) 2559 9973 Fax: (852) 2547 9528Email: [email protected]: www.wcn2013.org

45 February 2013 In Pract ice

Managing age-related macular degeneration

Age-related macular degeneration (ARMD) is the most common cause of irreversible loss of central vi-

sion in people beyond the age of 50 in the developed world. [BMJ 2003;326(7387):485-8] Asian studies show that its prevalence in Asians is largely similar. [Invest Ophthal-mol Vis Sci 2007;48:1007-11, Ophthalmology 2010;117(5):921-7]

ARMD is a progressive disorder and its diagnosis rests on signs in the macula. Dru-sen and changes in the retinal pigment epi-thelium (such as hyper- and hypopigmenta-tion) are the characteristic physical signs of ARMD. [New Engl J Med 2006;355:1474-85]

ClassificationTwo methods are used in the classification of ARMD – the widely used conventional meth-od, and that introduced in 1995 by the Inter-national Age-related Maculopathy Epidemi-ological Study Group (IARMESG). [Kanski JJ and Bowling B. Clinical Ophthalmology: A Sys-tematic Approach. 7th ed. UK: Elsevier Saun-ders; 2011:611-6, 620-7]

In the conventional method, ARMD is clas-sified into two types: dry or non-exudative ARMD, and wet or exudative ARMD. Dry ARMD, which makes up about 90 percent of diagnosed disease, has a more gradual pro-gression. Its advanced stage is characterized by geographic atrophy (GA). Wet or exuda-

tive ARMD is associated with rapid progres-sion of disease leading to visual loss. It is characterized by choroidal neovasculariza-tion (CNV), which is the abnormal growth of blood vessels (choriocapillaries) in the Bruch membrane, leading to pigment epithelial de-tachment. [Kanski JJ and Bowling B. Clini-cal Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, New Engl J Med 2006;355:1474-85, Exudative ARMD. Available at: emedicine.medscape.com/article/1226030 Accessed on 5 Decem-ber, Nonexudative ARMD. Available at: emedicine.medscape.com/article/1223154 Ac-cessed on 5 December]

The IARMESG classification divides ARMD into early ARMD, characterized by medium-large drusen, or by hyperpigmen-tation and/or small hypopigmentation; and

Dr. Shankari SothirachaganMedical Officer, Malaysia

46 February 2013 In Pract iceadvanced ARMD, which is more severe, with the presence of either GA or CNV. [Kanski JJ and Bowling B. Clinical Ophthalmology: A Sys-tematic Approach. 7th ed. UK: Elsevier Saun-ders; 2011:611-6, 620-7] Visual symptoms are inconspicuous in the early stages of ARMD.

Drusen is extracellular yellowish colored material deposited beneath the retinal pig-ment epithelium (RPE). They become visible on ophthalmoscopy when their diameter ex-ceeds 25 µm. [Br J Ophthalmol 1999; 83:358-68] Drusen can be hard or soft. Although the underlying pathophysiology of hard and soft drusen is similar, from a clinical and histo-pathological point of view there is a clear distinction. [Kanski JJ and Bowling B. Clini-cal Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7] Hard drusen, which consist of hyaline mate-rial, are well-defined, substantially smaller and are associated with a lower risk of visual loss. Soft drusen (semi-solid deposits) can en-large and combine to cause elevation of the RPE and loss of vision.

Risk FactorsAge is a major risk factor (usually over 65). Other risk factors include gender (women are at higher risk), hereditary, cigarette smoking (which almost doubles the risk), hyperten-sion, diet (high fat intake and obesity) and lack of exercise. [Holz FG, Pauleikhoff D, Spaide RF and Bird AC (2004) Age-Related Macular Degeneration. Heidelberg, Germany: Springer-Verlag. Chapter 1: Epidemiology of Age-related Maculopathy. A review (pages 2-15), Kanski JJ and Bowling B. Clinical Oph-thalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Lancet 2012; 379: 1728-38] Cataract surgery, blue iris and high sunlight exposure are as yet uncon-

firmed risk factors. [Holz FG, Pauleikhoff D, Spaide RF and Bird AC. Age-Related Macular Degeneration. Heidelberg, Germany: Spring-er-Verlag; 2004:2-15, Kanski JJ and Bowling B. Clinical Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Age-related macular degeneration. Available at: www.rnib.org.uk/eyehealth/eyeconditions/conditionsac/Pages/amd.aspx Accessed on 5 December]

DiagnosisBoth dry and wet ARMD can be found in the same patient; one in each eye or both in the same eye. [New Engl J Med 2006; 355:1474-85] Patients with advanced ARMD or moder-ate loss of vision due to early ARMD in one eye have a 50 percent chance of developing ARMD in the other eye within 5 years. [Kan-ski JJ and Bowling B. Clinical Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7]

Dry ARMD tends to cause gradual, pro-gressive visual impairment, commonly over months to years. Patients complain of fluctu-ating vision [Kanski JJ and Bowling B. Clini-cal Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Exudative ARMD. Available at: emedicine.medscape.com/article/1226030 Accessed on 5 December] and gaps in an image. [New Engl J Med 2006; 355:1474 -85] Peripheral vision is usually retained. Small areas of geographic atrophy do not noticeably compromise good vision. Dry AMD may, therefore, remain un-recognized in its early stages.

Patients with wet ARMD present with a more rapid onset of painless blurring of cen-tral vision. They may complain of metamor-phopsia (image distortion) and central scoto-ma (partial loss of vision or a blind spot in an

47 February 2013 In Pract iceotherwise normal visual field) where visual acuity falls below the reading level and the legal driving level. [Kanski JJ and Bowling B. Clinical Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Exudative ARMD. Available at: emedi-cine.medscape.com/article/1226030 Accessed on 5 December]

Fluorescein angiography (FA), a method for examining the intraocular vascular beds, is used to confirm a diagnosis of CNV. Indo-cyanine green angiography (ICGA) uses an intravenous dye with different characteris-tics from FA (eg, less melanin absorbance) and it has an increased sensitivity in the de-tection of CNV. Optical coherence tomogra-phy (OCT), a newer optical imaging method, is now widely used for early diagnosis and progression of CNV and patient’s response to therapy. [Kanski JJ and Bowling B. Clini-cal Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Lancet 2012;379:1728-38] Fundus au-toflourescence imaging is another new non-invasive method now increasingly used clinically for characterization of geographic atrophy. [Kanski JJ and Bowling B. Clinical Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Exudative ARMD. Available at: emedicine.medscape.com/article/1226030 Accessed on 5 December]

ManagementARMD is managed by prevention in the early stages and treatment to ameliorate symptoms if late-stage complications occur. Prophylactic dietary supplements contain-ing high-dose antioxidants and minerals (vitamins C and E, beta-carotene, and zinc) can help delay progression of ARMD from intermediate to advanced stages. [Arch Oph-

thalmol 2001;119:1417-36] Modification of lifestyle-associated risk factors (smoking, lack of physical exercise, obesity) should also be recommended. [Kanski JJ and Bowling B. Clinical Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, Arch Ophthalmol 2003; 121:785-92] Pa-tients may be provided with Amsler grids for self-testing at home on a weekly basis to monitor disease progression. [Kanski JJ and Bowling B. Clinical Ophthalmology: A System-atic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7]

Monotherapy with an anti-vascular endo-thelial growth factor drug (injected into the vitreous) is the current standard of care for wet ARMD. Pegaptanib was the first anti-VEGF agent authorized for ocular treatment. However, ranibizumab and bevacizumab are currently used. Ablation of the area of neovascularization with thermal laser (laser photocoagulation) or induction of vascular thrombosis by photodynamic therapy PDT) with verteporfin, though less effective than anti-VEGF therapy, remain useful under certain clinical settings, particularly when anti-VEGF therapy is contraindicated or in-effective. [Kanski JJ and Bowling B. Clinical Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7, BMJ 2010; 340:c981] Combination therapy includes variations of anti-VEGF agents, PDT and steroids. [Kanski JJ and Bowling B. Clini-cal Ophthalmology: A Systematic Approach. 7th ed. UK: Elsevier Saunders; 2011:611-6, 620-7]

Visual impairment from AMD can lead to significant functional loss, reduced quality of life and depression. Early detection and prevention are critical. Any patients who present with blurring, distortion or loss of central vision should be promptly referred to an ophthalmologist.

48 February 2013 Humor

“My husband is not feeling well. He complains about his knees, his back, just about everything. Where do you think I can find

a pair of earplugs?”

“Wait a minute! Did you by any chance touch those little things

on my desk that look like candy?”

“I sent your brown suit to the cleaners. It will match the mahogany casket perfectly!”

“That anger management group you recommended ... Well, I was

there and it made me very angry!”

“A date with Pamela Anderson? By all means, go for it!”

“It’s your dentist Larry. He’s here to remind you that

it’s been 6 years!”“Allow me to introduce myselves!”

“If you are afraid of catching the flu, perhaps you should stay home!”

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Vietnam : Nguyen Thi Lan Huong, Nguyen Thi My Dung Tel: (848) 3829 7923 Email: [email protected]

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Medical Tribune is published 12 times a year (23 times in Malaysia) by UBM Medica, a division of United Business Media. Medical Tribune is on controlled circulation publication to medical practitioners in Asia. It is also available on subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy. Editorial matter published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is ac-curate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the informa-tion or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions.

© 2013 UBM Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechani-cal, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is com-mercial in nature.

Philippine edition: Entered as second class mail at the Makati Central Post Office under Permit No. PS-326-01 NCR, dated 9 Feb 2001. Printed by Fortune Printing International Ltd, 3rd Floor, Chung On Industrial Bldg, 28 Lee Chung Street, Chai Wan, Hong Kong.

ISSN 1608-5086

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