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July 2012

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OSA can be successfully managed in primary care

FORUM Surviving the approaching tsunami of diabetes

IN PRACTICE Therapeutics in osteoporosis

CONFERENCE Promising drug combination for breast cancer

NEWS Chengdu Land of Tea, Tao and Pandas

July 2012

OSA can be successfully managed in primary care


Rajesh Kumar
atients with obstructive sleep apnea (OSA) can be successfully managed in primary care by suitably trained GPs and nurses, according to Australian researchers. Previous studies have shown that ambulatory models of care for OSA in specialist clinics can produce patient outcomes comparable to laboratory-based management. However, this is the first randomized controlled study to be conducted in primary care. Researchers randomized 155 patients with OSA to either primary care-based management or usual care in a specialist sleep center. At 6 months, mean change in Epworth sleepiness scale (ESS) scores, the primary outcome measure of the study, was similar in the two groups (4.9 in the primary care group vs. 5.1 in the specialist group). GPs identified patients with symptomatic, moderate-to-severe OSA using a four-item screening tool, the ESS, and home oximetry. Primary care-based management was led by the patients GP and a community-based nurse and involved use of home auto-titrating of continuous positive airway pressure (CPAP). Usual care in a specialist sleep center involved management by a sleep physician and laboratory-based testing. In addition to similar changes in ESS scores at 6 months, mean change in Functional Outcomes of Sleep Questionnaire (FOSQ) score was similar in the two groups (2.3 in the primary care group vs. 2.7 in the specialist group), as was compliance with CPAP. Mean daily use of

A randomized study involving 155 patients with OSA has shown that a primary care-based management approach can produce outcomes comparable to usual specialist care.

CPAP was 4.8 hours in the primary care group and 5.4 hours in the specialist group. Within-study costs for primary care management were lower than those for specialist care, with significant savings of A$2,157 (95% CI: A$1,293 to A$3,114) per patient. With the rise in demand and growing waiting lists for sleep physician consultation and laboratory-based sleep services, there has been increasing interest in development of ambulatory strategies for the diagnosis and management of OSA involving home sleep monitoring and auto-titrating CPAP, said lead author Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at Repatriation General Hospital, Adelaide, Australia. The results showed that a simplified approach for the treatment of OSA in primary care was not clinically inferior to manage-

July 2012 betes were treated only by specialists, but are now commonly managed in primary care. Dr. Ong Thun How, director of the sleep disorders unit at Singapore General Hospital, agreed a greater role for GPs could be feasible, but said the awareness of OSA among them is still not very good due to insufficient exposure to various aspects of sleep medicine at undergraduate and postgraduate level. In an attempt to fill some gap, Ongs unit is organizing a sleep symposium on 13-14 October this year focusing on management and diagnosis of OSA and will also run a concurrent CPAP workshop that will help GPs learn how to manage patients on CPAP. The study findings may not be applicable to all as the participants were relatively well, community-screened patients. Those with more complicated disease, eg, respiratory failure and/or concomitant heart disease, will still probably need specialist care, Ong added.

ment of these patients in a specialist sleep center. These were recently presented at the American Thoracic Society international conference 2012 in San Francisco, California, US. This approach also offers a lower cost alternative to usual care. In addition, waiting lists for specialist sleep centers are long, and home care may be preferred by patients, said Chai-Coetzer. Rather than a move to transfer the management of OSA from specialist to primary care, he envisioned GP model of care to be complimentary to specialist care, with GPs working alongside specialists to help relieve the excess burden of untreated disease in the community and to expedite treatment. This would be particularly beneficial for rural and remote regions, as well as developing nations, where access to specialist services may be limited, he said, adding that historically, chronic conditions like asthma and dia-

July 2012

Forum

Surviving the approaching tsunami of diabetes


Excerpt from a speech by Ms. Geralyn R Spollett, American Diabetes Association (ADA) president of health care and education, during the ADAs 72nd scientific sessions held recently in Philadelphia, Pennsylvania, US.

ne person is diagnosed with diabetes every 17 seconds. This one person could be your family member, your child, or the man that rides next to you on the train to work each morning. For many of us, diabetes has been our lives work. Unfortunately, there is enough work in this field to last for generations to come. My fondest dream is to hold high the vial of a miraculous serum as Jonas Salk did when he announced the polio vaccine, and tell you that I and my colleagues have found a cure for diabetes and our mission is fulfilled: a life free of diabetes and all its burdens! However, lately I have been having two recurring nightmares. In one, there are lines and lines of people, all with diabetes, who are typing their name into a vast computer program. They fill out a questionnaire and then download a list of lab work to be done prior to their 3-minute telephone or online appointment time. The lucky ones will talk with a real person. The unlucky ones will get an automated response from a very clever program that allows them to select options, similar to the one employed by airlines. But instead of a voice asking you if you want flight information, it will ask you to click 1 if you need insulin or dietary adjustments. My second nightmare, unfortunately, is real. It is the story of a village in the Middle

Around 380 million people globally are expected to have diabetes by 2025.

East where persons with diabetes can buy only one vial of insulin. Each person gets their share of 20 units; just enough to keep them alive and functioning. When I hear that 380 million people in the world are expected to have diabetes by 2025, I dont see a number. I see people like my patients and these villagers who struggle everyday to live a life with a disease that demands so much and gives back so little. We are currently in the midst of a tsunami of diabetes. Its first wave is the ever rising wave of obesity, the underlying current of the increase in diabetes. Worldwide, 2.8 million people die as a result of being overweight or obese and the prevalence of obesity has doubled between 1980 and 2008. North America leads the trend with more than 30

July 2012

Forum
clinicians and educators to help reduce the impact of diabetes by supporting research into prevention, cure and care of those already affected, and by increasing the resources devoted to research. Research shows that despite comparable diabetes care, some groups have poorer health outcomes than others. Factors such as physician interaction, prevalence of undiagnosed or untreated depression, fewer resources, greater stress associated with socioeconomically deprived neighborhoods and out of pocket costs are important for determining outcomes. Improved healthcare delivery systems must, therefore, focus on making it more cost effective and easier to deliver diabetes care within primary care settings, with easier access to self care plans. Ongoing support for self-care in the form of newsletters, email, social media, community board postings, access to information lines and diabetes educators is absolutely necessary. Currently, access to these programs is limited in the government and private sectors. The next step is to take to the higher ground, ie, making change happen. That is the ethical and the right thing to do. If every single one of us was able to inform the public and heighten the awareness of the dangers of a growing diabetes epidemic, just think what we could accomplish. We are all stakeholders in our healthcare system: whether researcher, educator or clinician. The current healthcare systems respond best to acute and episodic care. But that model will not address the burgeoning needs of a population requiring chronic care. Change must start here and now, with those of us who are touched by diabetes and have made it our lives work.

percent people being obese, closely followed by the tip of Africa and the Middle East. Asia and Europe are close behind, with a prevalence of between 20 to 29 percent obesity. The second wave is hyperglycemia. Worldwide, the alarming rise in the incidence of hyperglycemia closely follows the obesity trend and these show no signs of abatement. According to the International Diabetes Federation, there were 284.6 million people with diabetes worldwide in 2010, which is expected to grow to 438.4 million by 2030. The greatest increases will occur in Africa and the Middle East. In North Africa, greater than 90 percent increase is expected, followed by South East Asia and South and Central America. Not only is diabetes a healthcare crisis, it is also an economic one since it will send destructive shockwaves through economies. Diabetes affects the most productive age group of 40 to 59, which in turn affects gross national productivity. We must take the necessary steps to survive this tsunami by first sounding the alarm to warn the public of the dangers to come, preparing ourselves and the healthcare system to reduce the impact and, ultimately, taking to the higher ground. There is false information, misconceptions and myths about diabetes in every sector of our society, including amongst healthcare professionals. Diabetes is a disease without a face. Theres little recognition of its potentially life threatening nature or the demands of daily care. For the public, it is: Dont eat your sugar and take those (insulin) shots every day. But it is much more than just that. We must convince the public that diabetes is a serious disease, with serious personal and societal consequences. Next step is for

July 2012

Philippine Focus

New tax measure to ensure better health for Filipinos


Gabriel Angelo Sembrano, RN
n June 6, 2012, HB 5727 as amended, otherwise known as the Sin Tax Reform bill, was approved in a remarkable move by the Lower House. Certified as an urgent bill by President Benigno Simeon Aquino III, the passage of the law is now in the hands of the senators. The current sin taxes have already been frozen for 16 years due to the price classification freeze, which preserved low tax rates for all brands existing since 1996. According to Dr. Anthony Leachon, noncommunicable diseases consultant of the Department of Health (DoH), HB 5272 as amended aims to reduce consumption of these sin products. Health is the primary objective as we are not only talking about the health of one segment or market, but the health of a nation. He adds that the current tax rates have proven to be ineffective in curbing cigarette and alcohol consumption as it is shown that consumption is continuously on the rise. The significant tax increase is an attempt to catch up on the large health and economic costs, which, according to a study of Dr. Antonio Dans of the Philippine General Hospital, amounts to a minimum of P188 billion in 2011. This is due to tobacco-related deaths and diseases that low tax rates have caused the Philippines. Leachon mentioned that if the bill passes, funds generated will ultimately trickle down to the farmers and the general populace through the Universal Healthcare Program (UHC). Farmers will be assured of a safety net through programs that support

alternative livelihoods. The Filipino people, especially the poor, will benefit from better health facilities, enrollment in PhilHealth and other health-related gains. Our sin tax for tobacco is the lowest in Asia. The cost of cigarettes in the Philippines is the lowest in the region accounting for the prevalence rate of smokers among the young and the poor, Leachon pointed out. In effect, around 28.3% of the adult population smoke and an alarming 48% of teenagers engage in such practice. Currently on the average, 240 Filipinos die daily because of smoking-related diseases, Leachon added. This translates to 180 to 300 billion pesos a year in expenditures. Leachon noted that HB727 as amended is essentially progressive since there will be transfer of funds, which is around 33 billion pesos, from the sin tax to the sick, young and poor through the earmarking of funds for the UHC program. This will cushion the poor from the economic and health burdens brought about by consumption of sin products. The Philippines is a party to the Framework Convention on Tobacco Control (FCTC), the first international health treaty where we pledged to reduce smoking prevalence from 28.3% at present to 25% by 2014, according to Leachon. We need to inform and influence decision makers particularly the senators who will be reviewing and approving the sin tax bill. A collaborative and multi-sectoral approach is in order to push the bill to its fruition, Leachon said.

July 2012

Philippine Focus

CONFERENCE COVERAGE
42nd Philippine College of Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

High prevalence of coronary artery disease seen in adults with CHD


Dr. James Salisi

study by Dr. Melgar Matulac et al., revealed high prevalence of coronary artery disease (CAD) among adult patients with congenital heart disease (CHD) in a review of patients who underwent coronary angiogram at the University of the Philippines-Philippine General Hospital from 1998 to November 2012. Spurred by the scanty data on the prevalence of CAD in adults with CHD, the investigators found a higher prevalence of CAD at 11.5% than the general population. This is an important finding since coronary angiography is not routinely done in adult patients with CHD and could potentially alter survival outcome by mitigating complications of CAD through early detection and treatment. The study aimed to define the risk for myocardial ischemia as the risk of acquiring coronary artery disease increases with age; the survival outcomes of patients with congenital heart disease reaching adulthood has steadily improved. Past studies have only concentrated on hemodynamic aspects of the congenital lesions resulting in scanty data on the burden of CAD in adults with CHD. In this study, 90 adults with CHD who underwent hemodynamic assessment and interventions at the UP-PGH Catheterization laboratory from 1998 to 2011 were initially included. Fifty two underwent coronary angiog-

raphy and 52 percent of this cohort who were 40 years old and above underwent routine diagnostic assessment to rule out presence of coronary artery disease prior to planned interventions. Patients with all types of CHD were included and classified as simple, intermediate or complex CHD. Significant coronary artery disease was found in 11.5 percent of patients who underwent coronary angiography. All of them were 40 years old and above, four of them are female, five of them had documented traditional CVD risk factors like hypertension. None of the patients with significant CAD had cyanosis while four patients had typical chest pain. Majority of CHDs were simple and comprised mostly of atrial septal defects (36%). Four (70%) patients with simple CHD and 2 (30%) with intermediate CHD had significant CAD, but patients with complex CHD had none. Patients with complex CHD rarely reach adulthood and this in part explains the zero incidence of CAD in this population. The prevalence of CAD in adults with CHD is higher in this study than in the general population without suspicion of CAD of similar age. The absence of cyanotic patients was suggested to be due to its protective effects against coronary atherosclerosis.

July 2012

Philippine Focus
The findings of this study support the recommendation of routine coronary angiography among adult patients with CHD who are 35 years old and above and with traditional cardiovascular risk factors. The study bolsters the case for primary prevention of CAD and modification of traditional CV risk factors applied to the general population.

Systemic arterial hypertension was the most common risk factor. Other risk factors were dyslipidemia and diabetes. Smoking history is present in 1 in 5 of those with CAD. Patients with significant CAD in this study had at least one cardiovascular risk factor, which highlights the need for primary prevention of CAD in adults with CHD.

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July 2012

Philippine Focus

CONFERENCE COVERAGE
42nd Philippine College of Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

Proper diagnosis drives therapy in pulmonary arterial hypertension


Dr. Yves St. James Aquino
iagnose early and differentiate pulmonary arterial hypertension (PAH) from pulmonary hypertension (PH) for better management, recommended Dr. Darren Taichman, senior medical associate under the Medical Education Division of the American College of Physicians. According to consensus guidelines, pulmonary hypertension is hemodynamically defined as mean pulmonary arterial pressure of >25 mmHg, while pulmonary arterial hypertension is defined as pulmonary arterial pressure of >25 mmHg with normal pulmonary capillary wedge pressure or left ventricular end-diastolic pressure of <15 mm Hg. Although we define (PAH) hemodynamically, in fact, the effect of the disease is really on the right heart. Thats what drives all the symptoms, said Taichman. Typical progression of PAH involves continuous increase in pulmonary vascular resistance over time, with subsequent increase in pulmonary arterial pressure, said Taichman. Eventually, as the PVR increases, PAP will drop, which might give the impression that the patient is getting better. Whats happening is that the right heart initially compensated and able to handle that rising resistance, and then it starts to fail. The patient develops symptoms and can no longer generate the increased pressure to overcome this ever increasing resistance, said Taichman. Despite the progress in recognizing the disease, the prognosis is still poor as most cases

are diagnosed late, according to Taichman. Delay in diagnosis may account for the fact that PAH has no specific symptoms associated with it. Presenting symptoms such as dyspnea (84%), fatigue (29%) or angina (20%) are seen in other diseases. Taichman added that most physicians who do diagnose pulmonary hypertension fail to differentiate it from PAH. Pulmonary arterial hypertension is one of the rarest of the types of pulmonary hypertension, which also include left heart disease, hypoxemic lung disease, thromboembolism and other hematologic and oncologic diseases. Since diagnosis drives therapy, it is important to gather information from medical history and diagnostics. Suspect PAH when there is a family history of PAH or death due to non-specific cardiac cause, a medical history of congenital heart disease or non-responsiveness to traditional medication. Diagnostics that may hint the cause or type of pulmonary hypertension include echocardiogram, electrocardiography, chest x-ray, sleep study to rule out sleep disorders, ventilation-perfusion scan, CT scan, right-sided cardiac catheterization, autoantibody and HIV tests and laboratory exams that check cirrhosis and portal hypertension. Supportive therapies in PAH may include digoxin, oxygen and anticoagulation. Approved therapies include prostanoids, endothelin antagonists and type 5 phosphodiesterase (PDE-5). The choice of treatment should depend on the severity and the risk level of the disease, said Taichman.

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Philippine Focus

CONFERENCE COVERAGE
42nd Philippine College of Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

Preemptive platelet transfusion not needed for acute dengue infection


Gabriel Angelo Sembrano, RN
rophylactic platelet transfusion for patients treated for acute dengue infection did not demonstrate significant benefits over other treatment modalities, according to a retrospective cohort study conducted at the United Doctors Medical Center (UDMC) by Dr. Edgel Nazareno et al. The main objective of the study is to elucidate that prophylactic platelet transfusion brings considerable positive effects on patients with acute dengue infection. In obtaining the socio-demographic data, signs and symptoms present, treatment and clinical outcome data, the investigators reviewed a total of 149 medical charts of patients aging 19 years old and above who were admitted at the UDMC from July 1, 2009 to June 30, 2011, presenting with acute febrile disease lasting for 2 to 7 days and falling under the case definition for dengue hemorrhagic fever or dengue hemorrhagic syndrome by the World Health Organization. Not included were patients who had other active infections such as pneumonia, UTI, tonisillitis, typhoid fever, etc. Also excluded from the study were those who had unstable co-morbidities like stroke, diabetes mellitus, hypertension, liver cirrhosis and other liver diseases that can alter the course of the infection. Patient records were then grouped into three categories: patients who were observed with strict monitoring of the level of hydra-

tion (group 1), patients given platelet transfusion as prophylaxis even without signs of active bleeding (group 2), and patients given platelet transfusion as therapeutic for patients with signs of active bleeding (group3). Based on the generated results in the study, hematocrit levels prior to platelet transfusions, group 2 presented with the highest level (0.45 versus 0.41 for groups 1 and 3; p=0.001). The white blood cell count and proportion of subjects with >0.50 hematocrit level were essentially the same among the three groups. The lowest level of platelet count reached was significantly greater in group 1 than in the two other groups, while groups 2 and 3 did not show significant difference. At the time of platelet transfusion, difference in the platelet count between groups 2 and 3 were borderline significantly different with a trend towards higher count in group 3 than in group 2. In terms of the length of stay of patients in the hospital, group 3 showed significantly longer stay when compared to group 1 but not with group 2, while groups 1 and 2 did not have any significant difference. The researchers concluded that prophylactic platelet transfusion in cases of acute dengue infection does not present added benefits for patients over other treatment modalities. The World Health Organization stresses that prompt and rapid resuscitation from shock and correction of metabolic and electrolyte imbalances prevent disseminated intravascular coagulation.

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July 2012

Philippine Focus

CONFERENCE COVERAGE
42nd Philippine College of Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

Specialist warns against the dangers of sleep apnea


Gabriel Angelo Sembrano, RN bstructive Sleep Apnea (OSA) is a potentially life-threatening disorder, said Dr. Virginia de los Reyes of San Juan de Dios Hospital. Usually marked by loud snoring, patients with OSA have 2 to 7 times the risk of figuring in vehicular accidents due to loss of alertness than those without such disorder. In addition, there is also higher risk for complications, like systemic hypertension, pulmonary hypertension, myocardial infarction, cerebrovascular diseases, cardiac arrhythmias and metabolic syndrome. In reality, the OSA patients do not actually visit clinics with complaints of snoring, or apnea even. They usually come to our clinics because they are already suffering from cardiovascular complications. So, it is the role of the internists to try to dig deeper if they have underlying OSA and be able to manage it properly, de los Reyes said. According to de los Reyes, OSA is one of the most common sleep disorders characterized by repetitive episodes of upper airway obstruction that occur during sleep and is associated in the reduction of blood oxygen saturation. This is usually caused by decrease in muscle tone, increased soft tissue around the airway or structural features that give rise to narrowed airways like enlarged tongue or enlarged tonsils that eventually reduce the

cross-sectional area of the upper airway lumen. In diagnosing OSA, de los Reyes stressed that polysomnography (overnight sleep study) is the gold standard diagnostic test. This test does not only confirm the diagnosis, but it also determines the severity of the disease and the best management approach. For treatment, de los Reyes advises patients to lose weight, especially those who are obese. We try to tell them to keep their weight at a normal BMI, said de los Reyes. She also recommends postural therapy where patients with OSA sleep on their side, So there is a

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The mortality risk increases for those OSA patients without treatment but it becomes similar to the general population when they are compliant with CEPAP, said de los Reyes. For mild OSA, other non-invasive treatment options are available, such as tongue retaining device and mandibular positioning design. In some cases where the noninvasive treatments fail, surgery could be an option for correctable abnormalities like enlarged tonsils.

small propensity for their tongue to fall backwards and block the airway. De los Reyes pointed out that the gold standard for treatment of moderate to severe OSA is continuous positive airway pressure (CEPAP). In CEPAP, [the] machine blows air to a tube and the tube is connected to a nasal or facial mask. The air is transmitted to the airway and it acts as a pneumatic splint opening the obstructive airway. With this, the patient is able to breathe properly, de los Reyes said.

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July 2012

Philippine Focus

CONFERENCE COVERAGE
42nd Philippine College of Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

Resistant hypertension remains a challenge


Dr. James Salisi
esistant hypertension remains a challenge and this is expected to become more so as the population is aging, said Dr. Romeo Divinagracia from the Philippine Heart Center. He emphasized the need to identify resistant hypertension in patients for the quality of life and survival benefits that directed diagnostics and therapy may give them. A persistently elevated blood pressure above 140/90 mm Hg in spite of taking three antihypertensive agents of different classes including a diuretic defines resistant hypertension. It is primarily a systolic problem and is related to age. Difficult-to-treat hypertension is present in 30 percent of the geriatric population but only 5 percent have resistant hypertension, highlighting the need to differentiate true resistant hypertension from psuedoresistance. We need to identify patients who are at risk of having reversible causes of hypertension who may benefit from special diagnostics and therapeutic considerations, Garcia emphasized. Recommended workup of patients with resistant hypertension is a two-step process. First, confirm that it is indeed resistant hypertension by ruling out or correcting factors associated with pseudoresistance. Second, identify the true factors involved in treatment resistance.

Citing Garj et al., on the causes of resistant, Garcia pointed to drug-related causes in 58 percent, non-adherence to medications in 16 percent, and psychological causes in 9 percent of patients as the top three causes of resistant hypertension. Medication adherence is a common issue among hypertensive patients. Compliance with medication is difficult in many cases and this is unfortunate since 80-percent compliance is needed in order to have pharmacologic benefit. Exogenous substances like NSAIDS for arthritis and pains, symphatomimetic drugs like phenylephrine and steroids, and herbal preparation may raise the blood pressure in patients taking antihypertensive medications. Pseudoresistance may be caused by measurement artifact, white-coat hypertension, pseudohypertension and physician inertia. Improper BP measurement may give falsely elevated BP while psuedohypertension in the elderly is brought about by heavily calcified arteries that no amount of antihypertensive medication could adequately treat. Other diseases associated with resistant hypertension may include renovascular diseases, Cushings disease, tumors, genetic diseases and obstructive sleep apnea. Lifestyle causes include obesity, alcohol, drugs and high-salt intake.

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shown that in a period of over a year after denervation, there is a sustained and progressive reduction in both systolic and diastolic pressure. Surgical symphatectomy has reduced blood pressure in patients but may have intolerable side effects like urinary and sexual dysfunction. Baroreceptor stimulation by Rheos device inserted via the carotid nerves allow for personalization of treatment goals.

Patients may benefit from interventional management like renal symphatetic denervetion using radiofrequency ablation, surgical sympathectomy, and baroreceptor modulation. These modalities intervene at the anatomical level to reduce blood. Radiofrequency is used to ablate nerve fibers at the renal arteries adventitial layer. Although it is a difficult procedure to perform, it has been

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July 2012

Philippine Focus

CONFERENCE COVERAGE
42nd Philippine College of Physicians Annual Convention, 6-9 May 2012, SMX Convention Center

Dabigatran can be an alternative to enoxaparin for VTE, study says


Dr. Yves St. James Aquino

meta-analysis of controlled trials showed dabigatran etexilate as an effective alternative to enoxaparin in prevention of venous thromboembolism (VTE) after orthopedic surgery, according to a study done by Dr. Mary Shiela Ariola et al., of the Cardinal Santos Medical Center. Using Jadad criteria for evaluation, the meta-analysis included randomized, controlled trials published in PubMed and Medline involving an oral direct inhibitor, dabigatran etexilate, as an experimental drug that was compared with enoxaparin in the primary prevention of VTE in patients undergoing elective total hip and knee arthroplasty. Primary efficacy outcome is the major VTE events and VTE-related mortality; while the major safety outcome is the occurrence of major bleeding events during study treatment. Results showed that dabigatran 220 mg OD had significant benefit in preventing total VTE events and VTE-related mortality (RR-0.80; CI=0.60-1.06). Dabigatran 150 mg OD was proven to be less effective in

preventing total VTE events and mortality (RR=1.14; CI=0.83-1.57), but causes less bleeding events. Heterogeneity tests comparing both doses of dabigatran against enoxaparin in preventing VTE events showed that all the studies were homogenous. Similar results were seen in testing for the heterogeneity of dabigatran and enoxaparin in the occurrence of major bleeding events. The study suggested that dabigatran 220 mg OD is a safe, effective and possibly a superior alternative to enoxaparin for thromboprophylaxis in adults undergoing major lower limb orthopedic surgery. The study stated that according to the American College of Chest Physicians, postoperative VTE was the second most common medical complication and the second most common cause of excess length of stay. Use of thromboprophylaxis could provide benefit to patients, according to the study. Results of the meta-analysis indicate that oral dabigatran is a promising anticoagulant and alternative to enoxaparin in preventing major VTE events.

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NOTES ON LEADERSHIP
The Medical Tribunes Dr. Yves Saint James Aquino talks to presidents of specialty societies to discuss their roles in promoting their respective fields

General internists resuscitate a challenging field


11, 2011, PSGIM was officially founded. In building an organization that advocates internal medicine as a career, Dans could not help but emphasize the importance of primary care. All advanced countries are moving towards improving primary care. And to improve primary care, you need a good primary-care workforce. And to get a good primary-care workforce, you need people advocating careers in primary care, Dans said. This is one of the main reasons why Dans chose to practice general internal medicine in the first place. I went back to general IM because I was not happy with my career as a cardiologist. I felt compelled to ignore a lot of my patients symptoms, because I felt someone else should be looking at those symptoms. But what happened to those patients many times, their health fell apart, and I felt partly responsible, shared Dans. As a young organization, the society has come up with a three-point goal to help improve the practice, according to Dans. First, we have to make sure that we listen to and speak with our members. Thats communication between the leadership and the membership. Dans explained that they have the advantage of social media on their side, with a strong Facebook presence and a growing Web-page audience.

Dr. Antonio Dans


President Philippine Society of General Internal Medicine

he practice of general internal medicine (IM) has been facing difficulty with the trend of en masse subspecialization, and it was only logical for general internists to want to protect its field of practice. It has not been a part of the mission and vision of the Philippine College of Physician to advocate careers in general internal medicine. It is not in their explicit mission and vision statement. And so, this has been a neglected field, said Dr. Antonio Dans, founding president of the Philippine Society of General Internal Medicine. According to the societys website, in May of last year, 172 internists and three past presidents of the Philippine College of Physicians signed a manifesto calling for the formation of a new medical society. And on November

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We have convinced the PCP to require that all certified training programs around the country have at least one general internist, reported Dans. As the medical society turns to face the public, Dans could not have stressed it more, saying, They need us. The country needs us. But they dont know it yet. The country doesnt know it yet.

Second, to make sure to increase the supply of general internists and making sure its not just quantity, but quality. We want a supply of high-quality internists, he clarified. And lastly, Dans wants for the society to also work on the demand side. The society recognizes the need to work with PhilHealth, the Department of Health, and Universal Healthcare to help them understand the need for general internal medicine.

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ADVERTORIAL

Nutrient supplementation for healthier eyes and bones


s people age, physiological changes occur in the eye, including reduced peripheral vision and flexibility of the eye, degeneration of muscles of the eye and clouding of the lens.1 Age-related macular degeneration (AMD), the primary cause of irreversible blindness or severe vision impairment among the elderly, may also occur.2 Some of the risk factors for AMD include age, race (Caucasians), family history, co-morbidities like cardiovascular disease and hypertension, and smoking. Antioxidant vitamins and certain minerals have been found to decrease risk or progression of eye diseases. The Age-Related Eye Disease Study, which involved 4,757 elderly participants aged 55 to 80, evaluated the natural history and risk factors of AMD and cataract and how high doses of antioxidants and zinc may affect disease progression. Results from the study showed that high levels of zinc and antioxidants such as vitamin C, E and betacarotene significantly reduced the risk of advanced AMD and its associated vision loss.3 These antioxidants and zinc are said to be recommended for participants who have at least intermediate risk of developing advanced AMD.3 Besides visual changes, the elderly may also experience decline in bone mass, which often begins in the fourth decade. The linear decline in bone mass is at a rate of about 10% per decade for women and 5% per decade for men.4 Muscles, joints and bones go through physiologic changes as we age, and these changes

may lead to arthritis, postural changes, and even spontaneous fractures.5 Two nutrients essential for bone health are calcium and vitamin D, a vitamin that promotes intestinal calcium absorption and bone matrix mineralization. Studies have shown that reduced supplies of calcium are associated with decreased bone mass and osteoporosis, and a chronic or severe deficiency in the vitamin leads to osteomalacia, which presents with defective bone mineralization.6 Due to risk of skin cancer and other skin diseases, sun exposure as a main source for vitamin D is considered limited, and supplementation may be necessary to prevent vitamin D deficiency.6 Calcium supplementation has been found to reduce the rate of bone loss in osteoporotic patients, with more recent studies demonstrating a benefit not only on bone mass maintenance but also on reduction in fracture incidence. The best way to achieve adequate calcium intake is through the diet, but when dietary sources are scarce, supplementation may be necessary.6

References:
1. Smith S and Gove J. Physical Changes of Aging. University of Florida, IFAS Extension, 2010. 2. Woo JH. Singapore Med J, 2008;49(11):850. 3. Chew E. Use of Antioxidants, Vitamins, and Minerals in Age-Related Eye Diseases. NIH Publication accessed from http://ods.od.nih.gov/pubs/ elderly.14jan03.abst.chew.pdf last June 14, 2012. 4. Boss G and Seegmiller J. The Western Journal of Medicine, 1981;6(135):434-441. 5. Lata H. Ageing: physiological aspects. JK Science, 2007(9)3:11. 6. Gennari C. Calcium and vitamin D nutrition and bone disease of the elderly. Health Nutr. 2001 Apr;4(2B):547-59.

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BEYOND THE CLINIC

A surgeons pioneering work in medical informatics


Dr. James Salisi
n the Philippines, the name of Dr. Alvin Marcelo is synonymous to medical informatics, a field where he has done pioneering work by bringing the power of information communication technology to the practice of medicine. Marcelos interest in computers started early on in high school at the Ateneo de Manila where he was part of the first batch to have computer programming classes. He described ending up in medical informatics as a full big round circle for him. I placed computer science as my second choice in UPCAT. Biology as first choice (premed) and then checked the box for Intarmed, he said. He went into surgical training at the University of the Philippines-Philippine General Hospital (UP-PGH) after graduating from the UP College of Medicine. While surgery is not exactly the field that one would immediately associate with computers, Marcelo found that his passion for computing and the skills that he acquired in high school would become handy as he became the de facto computer troubleshooter among the residents of the Department of Surgery at UP-PGH. When I ended up in surgery (and surgery was one of the departments that could afford computers per division), I pulled out my high school skillsand my passion for computing was rekindled, he wrote through email.

Another UP Medicine graduate who attended a course on Medical Informatics at Stanford University, Dr. Cito Maramba, introduced Marcelo to the field that brings ICT and medicine together. After his training at UP-PGH and as a consultant of the Department of Surgery, Marcelo left the country for a two-year postdoctoral fellowship in medical informatics at the US National Library of Medicine in Bethesda, Maryland. His areas of research interests were in telepathology, mobile computing, and bibliometric analysis of MEDLINE content.

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I think the surgical training contributed to the discipline I needed to be CIO, he said. Approaching a problem as a team and having a leader to determine the plan of action to solve the problem are some of the similarities between the practice of surgery and informatics. But Marcelo thinks that in surgery the roles are predetermined, in contrast to informatics where the roles are not yet clear. While operating, you presume [team members] are carrying out their tasks as you have agreed upon. The good thing about surgery is that all of these roles are pre-determined (meaning most everyone know what theyre supposed to do by tradition). In informatics, these things are not yet explicit and must be explicated. But were getting there, he said. He thinks that the Philippines, while late in adopting eHealth, is now in golden period where the benefits of IT can be maximized to improve efficiency in the delivery of care. Marcelo opined that the government needs to create an enabling environment to take advantage of this opportunity where costs of ICT have gone down, people are IT-aware, and almost everyone is already open to the benefits of ICT in health. That is what I want to achieve right now the creation of that environment where the many potential players of eHealth in the country (government, private sector, academe, NGO, patients, etc.) can collaborate and create systems and subsystems that make for more affordable quality health care especially for the poor, he said.

Upon coming back, he established the Master of Science in Health Informatics at the UP Manila, a pioneer program in graduate health informatics education. Together with other physicians and health workers and with the help of Pasay City health department, he helped create and manage the Community Health Information Tracking System or CHITS, a multi-awarded IT application and the Philippines first electronic medical record system for rural health clinics. He has worked in various projects that used IT as a tool for better information management and has been an advocate of the use of free and open source software in the information systems in public service. In 2005, because of his work in the use of open source software in his community health-based projects, Marcelo was awarded by the Philippine Jaycees as one of the Ten Outstanding Young Men in the field of medical/health information. After serving in different positions in the state University and various non-government projects, he served as the director of the National Telehealth Center, the pioneer research and development center on the use of ICT for health and development. He now serves as chief information officer (CIO) of PhilHealth. Marcelo finds that even though he remains a consultant at the Division of Trauma under the Department of Surgery at UP-PGH, he does not practice surgery in the strictest sense anymore. But he sees surgery at the core of what he does in terms of diagnosing a problem, crafting a solution and thinking of what problems he will encounter, during and after.

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TREATMENT FOCUS: Endocrinology and nephrology

Hypoglycemia in the emergency room


Dr. Adrian Paul Rabe
iabetes mellitus (DM) has profound effects on small and large vessels, causing microvascular and macrovascular complications. Aside from these chronic problems, diabetes also causes other conditions that have to be recognized and treated rapidly, known as diabetic emergencies. These are diabetic ketoacidosis, hyperglycemic hyperosmolar state and hypoglycemia. Among the three, hypoglycemia is considered to be the most dangerous. Recently, hypoglycemia, defined as blood sugar 70 mg/dL, was touted as one of the reasons for the controversial exit of former Chief Justice Renato Corona during the impeachment trial. The paradox of hypoglycemia in diabetes Since diabetes is a disease of elevated blood sugar, patients often ask why they are at risk for hypoglycemia. The answer is actually simple: these patients receive medications that lower blood sugar. Harrisons Principles of Internal Medicine (HPIM, 18th edition) reports that hypoglycemia is most commonly a result of the treatment of diabetes. The main risk factors of hypoglycemia in diabetes are related to relative or absolute insulin excess. Errors in insulin administration, poor or erratic glucose intake, alcohol intake (that reduces liver production of glucose) and renal failure (that reduces insulin clearance) are likely causes of low blood sugar.

Dr. Aldrin Loyola, an expert in adult medicine from the University of the Philippines Philippine General Hospital, adds that hypoglycemia is further exacerbated when the defenses of the body against low blood sugar are compromised. The first defense is decreased insulin production that prevents uptake of glucose from the blood, while the second defense is increased glucagon which stimulates glucose production. The third defense is epinephrine, which increases liver and kidney production of sugar. If blood sugar still remains low, cortisol and growth hormone are released to increase glucose production further and decrease glucose utilization. Clinical clues to hypoglycemia When sugar is still above 50 mg/dL, the body develops signs and symptoms that signal the patient that blood sugar is dangerously low. Adrenergic symptoms include palpitations, tremors and anxiety. On the other hand, sweating, hunger and paresthesias are considered cholinergic symptoms. Patients with diabetes may have attenuation of these responses due to a reduced sympathoadrenal response. This situation where the patient does not recognize the hypoglycemia episode is called hypoglycemia unawareness. If the blood sugar remains uncorrected and dips below 50 mg/dL, diabetics develop neu-

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actionary increase in insulin which may provoke further hypoglycemia, which decreases its value in Type 2 DM. Thus, one should consider these factors before deciding to give glucagon. Once glucose is raised, an IV drip of glucose may be started to stabilize glucose concentrations. Tapering and adjustment of this drip is dependent on serial glucose measurements, which may be done using capillary blood glucose. Doing hypoglycemia justice After stabilizing the patient, further investigation as to the cause of the hypoglycemia may be performed especially if the low sugar is not explainable simply by poor intake, or medications. C-peptide levels measure insulin production by the body and may be elevated in patients with Insulinoma. Critical illnesses, such as sepsis or heart failure, are second to medications as the cause of hypoglycemia. Alcohol causes low blood sugar, usually after a several-day binge during which there is very little intake of food. Loyola adds that other drugs are associated with hypoglycemia, such as angiotensinconverting enzyme inhibitors, angiotensin receptor blockers, beta-adrenergic receptor blockers, quinolones and sulfonamides. Clinicians thus have to be vigilant about the signs and symptoms of hypoglycemia especially among diabetics. Prompt recognition and treatment are ways we could do justice to these individuals with low blood sugar.

roglycopenic symptoms from glucose deprivation of the brain. These include behavioral changes, seizures and decreased states of consciousness. Loyola says that the diagnosis of hypoglycemia is confirmed through the presence Whipples triad, comprised of symptoms of hypoglycemia, low plasma glucose (not a capillary blood glucose determination), and relief of symptoms after plasma glucose is raised. Thus, if possible, given the patients circumstances and urgency, blood must be drawn for examination before any efforts to increase sugar. Reversing hypoglycemia The first-line treatment of hypoglycemia is oral administration of glucose. Glucose tablets, glucose-containing fluids, candy or even food may be given as long as the patient is able to take those forms of sugar. Because of the risk of aspiration, patients with neuroglycopenia should receive parenteral therapy. A bolus of 25 g of glucose may be given intravenously (IV). A commonly supplied form of parenteral glucose would be a vial of D50-50, which contains 25 g of glucose in 50 mL of sterile water. Such an IV bolus should be given slowly to minimize irritation of the vein. If glucose is not raised by these measures, parenteral glucagon may be given using a 1-mg dose. The action of this hormone is to promote glycogenolysis, thus rendering it futile in patients with depleted glycogen stores. Loyola warns that glucagon also causes a re-

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TREATMENT FOCUS: Endocrinology and nephrology

The risks involved in kidney donation


Dr. Adrian Paul Rabe
idney donation is a prickly issue due to certain ethical considerations. It must be performed without seeking to dehumanize the donor and devalue the act of donation, as recognized by Dr. Beatrice Concepcion, a transplant nephrologist from Makati Medical Center and Medical Center Manila. Potential living donors should voluntarily offer to donate their kidney. They may not be coerced nor are they allowed to receive any monetary compensation. In the Philippines, there must be an established relationship between the living donor and the recipient, be it by blood or an emotional relationship, shared Concepcion A donor advocate may be recruited during decision making to ensure that a fully informed consent was taken, usually with family members taking part. All throughout the process of donation, counseling should also be performed. These measures ensure that there would be no exploitation in organ donation. In contrast, other countries allow altruistic donations aside from directed donations. Rigorous donor Selection Donor assessment is a meticulous process, taking 4 to 8 weeks. ABO compatibility (+/- HLA sensitization) is confirmed to initiate assessment. A complete history and physical examination must be performed to detect subtle signs of disease, including a risk assessment for tuberculosis, malaria, hepatitis virus and HIV. Diagnostic regimen should be able to screen subclinical diseases that adversely affect donation outcomes. Results of tests are analyzed

with the clinical examination to create a global assessment of the donor, which determines whether or not donation can proceed. Post-donation care The immediate post-operative survival of donors approaches that of any surgical procedure under general anesthesia, with mortality at 0.03 percent. The most prominent problem is usually post-operative pain so they are usually sent home on pain medications. Practices vary depending on the transplant center but donors can be discharged a few days after donation, notes Concepcion. Follow-up consults of donors are done at 2 weeks, 1 month and 6 months. Concepcion reiterates, Donors who were screened appropriately prior to donation do very well, with excellent kidney function many years after transplantation. Donating improves donor survival? Surprisingly, studies have shown a small reduction in mortality for kidney donors. This is attributable to the more conscientious efforts made by donors to maintain their health after the loss of one kidney, including a balanced diet and exercise to prevent diabetes, hypertension, and obesity. One of the specific lifestyle recommendations is to avoid contact sports, as well as excessive intake of NSAIDs. Donation is an option of growing importance in the Philippines. A well-informed orientation to this process will help encourage living donors to give a part of themselves, in order to save a life.

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Conference Calendar
3rd National Prosthetics and Orthotics Convention July 4-6, 2012 Info: Philippine Academy of Rehabilitation Medicine Telephone: (02) 536 9605 Email: mp_casero@yahoo.com Venue: Manila Hotel, Manila 65th Annual Convention of the Philippine Association of Nutrition July 9-10, 2012 Info: Philippine Association of Nutrition, Inc. Cellphone: (0920) 286 1532 Email: pan@fnri.dost.gov.ph Website: http://pan.fnri.dost.gov.ph Venue: Dusit Thani Ayala Center, Makati City Psychological Association of the Philippines 49th Annual Convention Hosted by University of San Carlos August 15-17, 2012 Info: Psychological Association of the Philippines Telephone: (02) 453 8257 Email: pap_1962_08@yahoo.com Website: http://www.pap.org.ph Venue: Waterfront Hotel, Cebu City 13th Philippine Society of Allergy, Asthma and Immunology Biennial Convention September 3-4, 2012 Info: Philippine Society of Allergy, Asthma and Immunology Telephone: (02) 712 9432 Email: pasaai_1972@yahoo.com Venue: Sofitel Philippine Plaza, Pasay City 7th Biennial Convention, Society of Adolescent Medicine of the Philippines September 3-4, 2012 Info: Society of Adolescent Medicine of the Philippines Cellphone: (0947) 844 4318 or (0928) 507 5724 Email: sampi.secretariat@yahoo.com Website: www.samphilippines.com Theme: State of the Nations Adolescents Venue: Diamond Hotel, Manila

UPCOMING
10th Surgical Forum, Philippine Society of General Surgeons August 1-4, 2012 Info: Philippine Society of General Surgeons Theme: Redefining General Surgery Telephone: (02) 456 8411 Email: psgs_secretariat@yahoo.com.ph Website: http://www.psgs.org.ph Venue: SMX Convention Center Philippine College of Chest Physicians Midyear Convention 2012 August 2-4, 2012 Info: Philippine College of Chest Physicians Telephone: (02) 924 9204 Email: pccp@skybroadband.com.ph Website: http://www.philchest.org Venue: Legend Hotel, Puerto Princesa, Palawan

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MARKET WATCH
Centrum Silver promotes cardiovascular health in older adults
s we age, normal physiological changes occur, including atrophy of heart muscles, calcification of heart valves and loss of elasticity of blood vessels. Changes in the heart capacity result in reduced blood flow and decreased stamina, reduced renal and hepatic function and less cellular nourishment, and impaired blood pressure. Filipinos who are 40 years old and up are at risk of hypertension and lipid problems, which also increases the risk of heart disease. Maintaining a healthy diet along with regular physical activity could prevent an estimated 80 percent of premature heart diseases and strokes. Adding to the benefits of lifestyle modification, Centrum Silver contains required amounts of vitamins and minerals to support the cardiovascular health of adults aged 50 and up. It contains beta-carotene, selenium, and vitamins C and E are antioxidants that control free radical damage; and B vitamins such as folic acid and B6 and B12 that help in the regulation of plasma homocysteine levels to decrease the risk of atherosclerosis and other cardiovascular problems.

Philips launches latest ultrasound system

hilips, a world leader in healthcare solutions, is raising the bar for medical imaging with the Philippine launch of its latest ultrasound systemthe iU22 xMatrix with Vision 2012 upgrade. The technology delivers enhanced ultrasound image quality, allowing doctors to gather more precise information and give more confident diagnoses. The Vision 2012 features next generation 2D, 3D and 4D performance enhancements as well as an array of high-level imaging functions. The Auto Doppler capability automates repetitive manual tasks to speed up and simplify standard vascular exams, while the Philips Fetal Heart Navigator allows doctors to acquire the fetal heart volume in as little as two seconds. The Vascular Plaque Quantification (VPQ) on the other hand is a non-invasive tool that uses 3D technology to examine the arteries and determine whether or not a patient is at risk of stroke or cardiovascular disease. Photo shows Cellinjit Bhuttel, Ultrasound Clinical Applications Specialist for Philips Ultrasound in Southeast Asia, explaining in detail the functions and upgrades of the Philips iU22 xMatrix ultrasound.

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July 2012

Conference Coverage

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

Promising drug combination benefits HER2+ breast cancer patients


Radha Chitale

novel agent linking the antibody trastuzumab (Herceptin) to a potent chemotherapy drug improved progression free survival in women with HER2-positive (HER2+) metastatic breast cancer compared with standard therapy, according to interim results from the phase III EMILIA* trial. The new agent, called T-DM1, may also have positive implication for overall survival. T-DM1 is a brand new way of treating HER2+ breast cancer, said lead researcher Dr. Kimberly Blackwell, Duke University Medical Center in Durham, North Carolina, US. I think it is the first of many antibody drug conjugates to follow that will link a potent anti-cancer agent to the targeted delivery system of an antibody. The trial, supported by Genentech, included 978 women with confirmed HER2+ metastatic breast cancer who were on or had recently been treated with taxane and trastuzumab. Patients were randomized to infusions of the HER2 antibody trastuzumab linked to the microtubule inhibitor emtansine (trastuzumab emtansine, T-DM1) or oral lapatinib plus capecitabine. Median follow-up was just over 1 year for both groups. Median progression free survival improved 35 percent with T-DM1, 9.6 months versus 6.4 months with lapatinib plus capecitabine (P<0.0001). Overall survival at 1 and 2 years was 84.7 percent and 65.4 percent, respectively, in the T-DM1 group and 77 percent and 47.5 percent

in the lapatinib plus capecitabine group. Median overall survival was 23.3 months with standard therapy but was not reached in the trastuzumab group (P=0.0005). The novel trastuzumab emtansine combination appeared to be safe and well tolerated. Emtansine is too toxic to administer systemically and linking it to trastuzumab helps guide it to tumor cells with HER2 receptors. Fewer severe adverse events occurred in the T-DM1 group compared to the lapatinib group (40.8 percent and 50.0 percent, respectively) with thrombocytopenia and increased liver enzymes as the most common adverse events. T-DM1 really works in this patient population, said Dr. Louis Weiner, director of the Georgetown-Lombardi Comprehensive Cancer Center in Washington, D.C., US, and noted the previously limited targeted therapy options for breast cancer patients with progressive disease. The improved survival is particularly notable since effective palliative treatment of metastatic breast cancer has rarely been associated with improved survival in a refractory setting, he said. Blackwell said the novel agent should offer important therapeutic options for HER2+metastatic breast cancer patients.

* EMILIA: An Open-Label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine+Lapatinib in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer

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July 2012

Conference Coverage

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

Radiation therapy in childhood increases breast cancer risk


Radha Chitale

dult survivors of childhood cancers treated with radiation therapy have an increased risk of breast cancer, similar to that of women who carry BRCA gene mutations, even if the radiation dose was low. Prior studies showed girls treated with radiation to the chest have increased risk of breast cancer, but lead researcher Dr. Chaya Moskowitz, Memorial Sloan-Kettering Cancer Center in New York City, New York, US, said the comparison to risk from BRCA gene mutations is unknown. The researchers compared 1,268 female 5-year cancer survivors from the Childhood Cancer Survivor Study (CCSS) and 4,570 first-degree female relatives of women with breast cancer from the Womens Environmental Cancer and Radiation Epidemiology (WECARE) to estimate the incidence of BRCA-1 and -2 carriers. The rate of breast cancer in the general public was 4 percent by age 50, according to analysis of the Surveillance, Epidemiology, and End Results (SEER) study. Among the WECARE cohort, 324 women were diagnosed with breast cancer by median age 55. Cumulative incidence of breast cancer was 31 percent among those with BRCA-1 mutations and 10 percent among those with BRCA-2 mutations.

In the CCSS cohort, 175 were diagnosed with breast cancer at median age 38 with a median 23 years lag until diagnosis. Median follow up of study participants was 26 years. The overall incidence of breast cancer was 24 percent among girls who survived any type of cancer but the incidence among Hodgkins lymphoma (HL) survivors was 30 percent by age 50, similar to that of women with BRCA-1 mutations. Moskowitz said the discrepancy could be the result of a larger area of the chest exposed to radiation during treatment for HL, which increases the risk of breast cancer. Typically, people who receive radiation doses of 20 Grays (Gy) or more are currently recommended for cancer screening. However, Moskowitz said it was remarkable that women treated for cancers other than HL with moderate doses of radiation (10-19 Gy) to large areas of the chest also have elevated risk of breast cancer similar to that of BRCA-2. These women are not currently recommended for screening but Moskowitz suggested they would benefit from breast cancer surveillance strategies as their risk is higher than previously recognized.

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July 2012

Conference Coverage

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

Newer agents no better than paclitaxel as first-line breast cancer therapy


Elvira Manzano
wo relatively new drugs for patients with recurrent or metastatic breast cancer failed to beat old stand-by paclitaxel in a phase III cooperative group trial. Treatment with paclitaxel resulted in a longer median progression-free survival (PFS) of 10.6 months compared with 9.2 months and 7.6 months for novel nanoparticle albuminbound paclitaxel (nab-paclitaxel) and ixabepilone, respectively. Rates of peripheral neuropathy and hematologic toxicity were also higher with both agents than with paclitaxel. Neither weekly nab-paclitaxel nor ixabepilone is superior to weekly paclitaxel, said study author Dr. Hope Rugo, of the University of California, San Francisco, US. In combination with bevacizumab, weekly paclitaxel is the better tolerated drug. The study involved 799 patients with locally advanced or metastatic breast cancer and no prior chemotherapy randomized to nab-paclitaxel 150 mg/m2, ixabepilone 16 mg/ m2), or paclitaxel 90 mg/m2 (as a control) plus bevacizumab every 2 weeks. Each treatment cycle lasted for 3 weeks, followed by a 1-week break. The primary endpoint was PFS or time from randomization to disease progression or

death from any cause. Median follow-up period was 12 months. The study was powered to detect a hazard ratio of 1.36 (median PFS of 10 vs. 13.6 months). Ixabepilone was dropped earlier from the trial after it demonstrated significantly worse PFS. Our data showed that we should not simply assume that newer drugs are always better than the standard therapies for metastatic breast cancer, said Rugo. She explained that dosing schedules are constantly being examined and refined, new therapies tested, and molecular characteristics of tumors are looked at closely to determine the right treatment for the right patient, with least toxicities. However, she said nab-paclitaxel may be a useful alternative in patients who cannot tolerate paclitaxel or in a setting where paclitaxel is not readily available. The US Food and Drug Administration in November 2011 revoked bevacizumabs conditional approval as a treatment for metastatic breast cancer because of potentially serious side effects such as high blood pressure and hemorrhage. At that time, enrolment for the trial, called CALGB 40502/NCCTG N063H, had already started.

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July 2012

Conference Coverage

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

Afatinib delays progression in advanced lung cancer


Christina Lau

fatinib, an investigational drug that irreversibly blocks EGFR (ErbB1), HER2 (ErbB2), HER3 (ErbB3) and HER4 (ErbB4), significantly extended progression-free survival (PFS) vs the pemetrexed/cisplatin combination in LUX-Lung3 the largest and most robust phase III trial so far in EGFR mutation positive advanced lung adenocarcinoma. The oral pan-ErbB inhibitor was particularly beneficial for patients with deletion 19 or L858R common mutations that together accounted for 89 percent of all EGFR mutations in the trial. Unlike reversible EGFR tyrosine kinase inhibitors such as gefitinib and erlotinib, afatanib blocks the entire ErbB family of receptors permanently, said lead author Dr. James Yang of the National Taiwan University Hospital. While gefitinib and erlotinib has demonstrated significant benefit vs firstline chemotherapy, LUX-Lung3 is the first trial in EGFR mutation positive lung cancer to use pemetrexed/cisplatin as a chemotherapy comparator. The global trial included 345 treatment-nave patients from 25 countries who had stage IIIB (wet) or IV disease (median age, 61 years; ECOG performance status, 0-1; East Asians, 72 percent; never-smokers, 68 percent). Patients were randomized 2:1 to receive afatinib (40 mg) daily or pemetrexed (500 mg/m2) plus

cisplatin (75 mg/m2) q21d until progression. The trial met its primary endpoint of PFS. After a median follow-up of 8 months, patients receiving afatinib had a significant 4.2-month improvement in PFS. Median PFS was 11.1 months with afatinib vs. 6.9 months with pemetrexed/cisplatin [hazard ratio (HR) 0.58; P=0.0004], Yang reported. The 12-month PFS rate was 47 vs. 22 percent. Importantly, the PFS benefit of afatanib was consistent in all relevant subgroups, including gender, age at baseline, race (Asian or non-Asian), baseline ECOG performance status, and smoking history (never smoked, or smoked <15 pack-years and stopped >1 year). The benefit of afatinib was even greater in patients with deletion 19 or L858R [N=308], he continued. In these patients, afatinib doubled PFS to 13.6 months vs. 6.9 months with pemetrexed/cisplatin [HR 0.47; P<0.0001]. PFS rate at 12 months was 51 vs. 21 percent. Patients treated with afatinib also had a significantly higher objective response rate (56.1 vs. 22.6 percent with pemetrexed/cisplatin; P<0.001), a longer duration of response (11.1 vs. 5.5 months), and a higher disease control rate (90 vs. 81 percent). In patients with deletion 19 or L858R, the objective response rate was 60.8 vs. 22.1 percent (P<0.0001).

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events were as expected with EGFR-targeting therapies, and were manageable and reversible. It is also important to note that patients in the afatinib arm received 16 cycles of therapy, vs. 6 cycles in the pemetrexed/cisplatin arm. In LUX-Lung3, only 7.9 percent of patients discontinued afatinib due to treatment-related adverse events (vs. 11.7 percent with pemetrexed/cisplatin), and only about 1 percent discontinued the drug due to diarrhea.

In addition, afatinib significantly prolonged the time to deterioration of cough (HR 0.6; P=0.007) and dyspnea (HR 0.68; P=0.015). Patients treated with afatinib had better quality of life. Grade 3/4 adverse events that were increased with afatinib include diarrhea [14.4 vs. 0 percent], rash/acne [16.2 vs. 0 percent], stomatitis/mucositis [8.7 vs. 0.9 percent], paronychia [11.4 vs. 0 percent], and dry skin [0.4 vs. 0 percent], said Yang. These adverse

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July 2012

Conference Coverage

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

Regorafenib offers hope for GIST patients failing TKIs


Christina Lau

he multi-kinase inhibitor regorafenib may represent the first targeted treatment option for patients with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) whose disease progressed despite prior use of both imatinib and sunitinib, suggest results of a phase III international trial. The GRID (Regorafenib in Progressive Disease) trial included 199 patients from 17 countries who failed at least imatinib and sunitinib the only two drugs approved for GIST worldwide. Patients were randomized to receive either regorafenib 160mg once daily plus best supportive care (BSC) (N=133), or placebo plus BSC (N=66), on a 3-weeks-on 1-week-off schedule. The trial was unblinded on disease progression, when placebo-treated patients were eligible for crossover to openlabel regorafenib and regorafenib-treated patients were continued on the active treatment. On the next progression, patients were taken off treatment. The trial met its primary endpoint, as progression-free survival (PFS) was significantly and four times longer in the regorafenib arm. Median PFS was 4.8 months for regorafenib vs. 0.9 months for placebo, with a hazard ratio (HR) of 0.27 (P<0.0001), reported Dr. George Demetri of the Dana Farber Cancer Institute in Massachusetts, USA. PFS rates at 3 and 6 months were 60 vs. 11 percent and 38 vs. 0 percent, respectively.

The same PFS benefit was maintained in patients with KIT exon 11 (N=51) or exon 9 (N=15) mutation, the most common mutations in GIST. The HR was 0.212 and 0.239, respectively, he continued. Disease control and objective response were also better with regorafenib, at rates of 52.6 vs. 9.1 percent and 4.5 vs. 1.5 percent, respectively. Although overall survival (OS) favored regorafenib (HR 0.77), the difference between the two arms did not reach statistical significance as 85 percent of patients in the placebo arm crossed over to receive open-label regorafenib, pointed out Demetri. Regorafenib was generally well tolerated in the trial, with side effects similar to those of imatinib and sunitinib. The most common grade 3 adverse events were hand-foot skin reaction (19.7 vs. 1.5 percent), hypertension (22.7 vs. 3 percent) and diarrhea (5.3 vs. 0 percent). The side effects were all manageable with dose modifications. There were no significant differences in grade 4/5 adverse events, he noted. Positive results of the trial were submitted to regulatory authorities in March 2012. If approved, regorafenib will fulfill an urgent unmet need for GIST patients who have exhausted all other treatment options, he suggested. While imatinib and sunitinib have increased patient survival in metastatic GIST

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VEGFR-1, murine VEGFR-2, PDGFR-, RET, BRAF and FGFR-1 that appears to target GIST in a possibly more powerful way, making it a potentially significant new option to help patients.

from 3-6 months to 5 years or more, 85 to 90 percent of patients ultimately develop resistance to these tyrosine kinase inhibitors (TKIs) that target KIT or PDGFRA. Regorafenib is a structurally distinct oral inhibitor of KIT,

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July 2012

Conference Coverage

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

Better strategies needed for ALL in adolescents and young adults


Christina Lau

dolescents and young adults with highrisk acute lymphoblastic leukemia (ALL) have poorer survival and higher toxicity from treatment than their younger counterparts, according to new data from a major phase III study which highlights the need for better treatment strategies for this group of patients. Historically, ALL patients older than 16 years have an inferior outcome compared with patients aged 1 to 15 years because older patients have higher rates of relapse and toxicity, said lead author Dr. Eric Larsen of the Maine Childrens Cancer Program in Scarborough, Maine, US. In the Childrens Oncology Group (COG) study ALL0232, we tested dexamethasone vs. prednisone during induction and high-dose methotrexate vs. escalating Capizzi methotrexate plus PEG asparaginase during interim maintenance 1 in a 2 x 2 factorial design. For the fist time, patients aged 21-30 years were eligible for enrollment in an ALL study. ALL0232 was in patients with newly-diagnosed B-precursor high-risk ALL. Of a total of 2,571 eligible patients in ALL0232, 501 (20 percent) were adolescents and young adults aged 16-30 years. This represents the largest cohort of adolescent and young adult ALL patients to date in a single clinical trial, he said. Previously, observations about ALL outcome were

usually made by comparing one trial with another. In ALL0232, the number of patients receiving the same treatment was large enough to allow comparison within the same trial. At 5 years, ALL0232 patients aged 16-30 years had significantly poorer event-free survival (EFS) and overall survival (OS) than those <16 years (68.0 vs. 80.9 percent and 79.8 vs 88.4 percent, respectively; P<0.0001). Relapses were significantly more frequent in adolescent and young adult patients, primarily due to a higher rate of bone marrow relapse, reported Larsen. The 5-year cumulative relapse rate was 21.3 percent in patients aged 16-30 years, vs. 13.4 percent in those younger than 16 (P=0.002). Marrow relapse at 5 years was 15.3 vs. 9 percent (P=0.0007). Interestingly, central nervous system (CNS) relapse was similar between the two groups, being 5.2 vs. 3.7 percent (P=0.58) at 5 years, he continued. According to the investigators, the treatment strategy of the trial was to try to improve disease control in the CNS. In addition, significantly fewer adolescent and young adult patients achieved remission, defined as <5 percent marrow blasts at the end of induction (97.2 vs. 98.8 percent; P=0.0134). Post-induction remission deaths were significantly higher in those aged 16-30 years vs those <16 years (5 years, 5.5 vs. 2.1 percent;

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Conference Coverage
pared with previous studies, which showed EFS rates of 50-60 percent, remarked Larsen. However, our results suggest that we need to find novel agents that improve leukemia control with reduced toxicity.

P<0.0001), although there was no significant difference in induction mortality between the two groups (2.4 vs. 1.8 percent; P=0.36). Adolescent and young adult patients treated in ALL0232 had improved outcome com-

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July 2012

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

Feeding, not starving, tumors improves response to therapies and overall survival
Radha Chitale
ancer patients may live longer if their tumor microenvironment is normalized, rather than starved of blood and other nutrients, so that therapeutic treatments are more effective, said Professor Rakesh Jain, of the Steele Lab for Tumor Biology, Massachusetts General Hospital, Harvard Medical School in Boston, Massachusetts, US. This approach has implications for the half billion people worldwide with diseases characterized by abnormal vessels, he said. As tumors grow, vessels can become disorganized, misshapen or blocked, creating areas without oxygen. This hypoxic environment creates high interstitial fluid pressure and contributes to genetic instability, angiogenesis, resistance to cell death and metastasis. However, chemotherapy, radiation therapy and immunotherapy are demonstrably more effective when the tumor microenvironment is in a normal state. In a study of 30 patients with recurrent glioblastoma treated with an anti-vascular endothelial growth factor (VEGF), seven had increased tumor blood perfusion for more than 1 month, which was associated with increased survival of 6 months compared to patients in whose tumors blood perfusion remained stable or decreased (P=0.019). [Cancer Res 2012;72:402-407] Normalization induced blood flow has the potential to increase survival in patients,

Normalizing the tumor microenvironment may help enhance the efficacy of therapeutic treatments.

Jain said. However, dose matters when treating with anti-VEGF therapy to improve blood flow to tumors; too little anti-angiogenic agent results in no change to the blood vessels and too much leaves only a small window for normalization before excessive pruning and hypoxia set in. Smaller molecules, about 10 nm, were the optimal size for drug delivery to promote normalization and tumor response. Alleviating hypoxia in tumors makes the mass immunostimulatory, Jain said, and vessels are able to bring more T-cells to the tumor to increase the efficacy of immunotherapy. Five to 10 years from now we would see normalization be combined with a variety of immunotherapies, he said. Jain also noted that a similar normalization strategy could be used for lymphatic vessels and the tumor cellular matrix as well to improve perfusion and improve the efficacy of chemotherapy, radiation therapy and immunotherapy and overall survival.

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July 2012

Conference Coverage

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

Acute cancer drug shortages due to manufacturing, quality control


Radha Chitale
isrupted manufacturing and quality control are the main culprits behind the high volume of drug shortages in the US that have left many cancer patients without necessary treatment. Dr. Richard Schilsky, of the University of Chicago and chair of the ASCO Government Relations Committee, described recent unprecedented shortages of generic injectable drugs such as methotrexate that are mainstays of treatment for many cancers. Were never exactly sure when a generic drug is suddenly going to go out of supply, he said, which creates anxiety for patients and treatment planning difficulty for physicians. Hundreds of drugs have been in short supply in the US over the past year including methotrexate, used frequently for leukaemia, Doxil, which treats ovarian cancer, paclitaxel, used in a variety of cancers including breast cancer, mustargen, used to treat lymphoma, and fluorouracil, given for colorectal and other cancers, and is a key part of adjuvant therapy. Shortages appear to be most acute among community practices, where the majority of adults receive care, said Dr. Michael Link, of the Lucile Packard Childrens Hospital at Stanford University in California, US and ASCO president.

Dr. Sandra Kweder, deputy director of the Office of New Drugs at the US Food and Drug Administration (FDA), said disruptions at large manufacturers of sterile injectable drugs have the most impact. For example, closing a single facility that makes 30 drugs can lead to dozens of shortages. Contamination with glass or metal particles in vials of medicine can also compromise drug availability. Kweder said the FDA works with drug manufacturers to address shortages by encouraging early reporting of production difficulties so that the agency can source the same or alternative drugs from different companies, sometimes from overseas manufacturers in India or Australia, for example. Schilsky noted that cancer drug shortages do not appear to be a problem in overseas markets. Permanent solutions to drug shortages will likely require legislation to make 6 months notice for withdrawals or manufacturing interruption mandatory by drug companies, with penalties for non-reporting, Schilsky said. Dr. W Charles Penley, of Tennessee Oncology in the US and incoming chair of the ASCO Government Relations Committee, noted that drug shortages, particularly of widely used generics, impact clinical research as doctors are unable to use them as standard therapy to measure experimental drugs against. This could really slow down progress if we dont have access to these very standard and vital agents, he said.

38

July 2012

Conference Coverage

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

Bevacizumab slows down ovarian cancer progression


Elvira Manzano

dding bevacizumab to standard chemotherapy delayed cancer progression in women with platinum-resistant ovarian cancer, results of a phase III AURELIA* trial showed. Median progression-free survival (PFS) a primary endpoint of the study was 6.7 months for combination therapy compared with 3.4 months for chemotherapy alone. The objective response rate more than doubled with the addition of bevacizumab 12.6 percent to 30.9 percent (P=0.001). For the first-time in platinum-resistant ovarian cancer, we have been able to significantly improve progression-free survival with a combination therapy, said lead study author Dr. Eric Pujade-Lauraine, professor, Universit de Paris Descartes, France and head of the Group dInvestigateurs Nationaux pour lEtude des Cancers Ovariens (GINECO), a clinical trials cooperative group based in France. The risk of the disease getting worse was halved in patients treated with the combination therapy. This is a breakthrough and will definitely change the practice in treating patients with ovarian cancer. In the study, 361 women with epithelial ovarian, fallopian tube or primary peritoneal cancers that had not responded to platinumbased chemotherapy were randomized to receive standard chemotherapy or bevacizumab plus chemotherapy (with one of three

standard chemotherapy agents topotecan, liposomal pegylated doxorubicin or weekly paclitaxel). Secondary endpoints were objective response rate, overall survival, safety, and quality of life. After a median follow-up of 13.5 months, 91 percent of patients in the chemotherapyalone group had progressed compared with 75 percent in the combination therapy group. The difference translated into a 0.48 hazard ratio of progression (P<0.001). Data on overall survival is expected next year. Rates of hypertension and proteinuria were higher among the bevacizumab group than with the chemotherapy-only group but bleeding events, febrile neutropenia and congestive heart failure were the same. These adverse effects were consistent with the known effects of bevacizumab and the different chemotherapeutic agents used in the study. These results are very significant. The addition of bevacizumab offers a new treatment option for 20 percent of women who have primary platinum-resistant disease as well as those whose disease later becomes platinumresistant, Lauraine concluded. Bevacizumab is a humanized anti- human vascular endothelial growth factor A (VEGFA) monoclonal antibody (mAb) indicated for metastatic colon cancer, renal cancer, certain lung cancers and glioblastoma multiforme of the brain typically in combination with standard chemotherapy.
*AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

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39

July 2012

In Practice

Therapeutics in osteoporosis: What every GP should know


Associate Professor Leong Keng Hong
Consultant Rheumatologist, Gleneagles Medical Centre, Singapore Adjunct Associate Professor, Yong Loo Lin School of Medicine, National University of Singapore

wrist. Of these, hip fracture is the most severe as it is associated with poor or slow healing after a surgical repair. Pathogenesis of osteoporosis Inadequate peak bone mass and imbalances in bone resorption and bone formation lead to structural deterioration and eventually, osteoporosis. Lack of estrogen as a consequence of menopause increases bone resorption and decreases bone deposition. Calcium metabolism may play an important role in bone turnover, as well as deficiency in calcium and vitamin D. Diagnosing osteoporosis As in any asymptomatic disease, a high index of suspicion is needed to diagnose osteoporosis. Fracture history at any site, fall history, height reduction and reduced body mass index (BMI) are important indicators, but the most significant clinical risk factors for validating osteoporotic fractures are age and weight, which have become the basis of the Osteoporosis Self-assessment Tool for Asians (OSTA) test. The OSTA test determines a patients risk of developing osteoporosis (high, moderate or low) and helps a physician decide who to send for a bone mineral density (BMD) test. A score of >20 in the OSTA test means the patient is at high risk, 0-20 equals moderate risk and <0 means low risk. Patients at high risk, or at moderate risk with other risk factors, should take a BMD test using a dual-energy x-ray absorptiometry (DEXA) scan. DEXA gives both the T score (deviation from the mean of the peak bone

Osteoporosis: A silent epidemic Osteoporosis often called a silent disease is characterized by a low bone mass and deterioration of the bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. The condition primarily affects post-menopausal women, but may also affect elderly men. Bones undergo continuous remodelling through repeated cycles of destruction and rebuilding to prevent accumulation of bone microdamage. Osteoclasts and osteoblasts sequentially carry out resorption of old bone and formation of new bone. In the elderly and in post-menopausal women, the extent of bone resorption far exceeds bone formation, resulting in bone loss. If this continues over the years, the result is osteoporosis. Approximately 200 million women worldwide suffer from osteoporosis. It is estimated that by 2050, half of all fractures in the world will occur in Asia. In Singapore, the incidence of hip fractures rose five-fold to 403 cases per 100,000 in women >50, or eight times more than the breast cancer cases. Aside from hip fractures, the most common clinical outcomes of osteoporosis are fractures of the spine, pelvis, upper arm and

40

July 2012

In Practice

mass) and the Z score (identifies secondary osteoporosis). Negative T and Z scores indicate weaker and thinner bones than normal bones. The more negative the number, the higher the risk of a bone fracture. A T score between -1 and -2.5 indicates osteopenia, the beginning of bone loss. A T score below -2.5 indicates osteoporosis. Aside from abnormal BMD, diagnosis requires investigation of underlying causes. While BMD testing does not diagnose fractures, it helps predict the risk of bone fracture in the future and can be used to track bone density changes over time. The FRAX algorithm calculates both the 10-year major osteoporotic and hip fracture risks of an individual and helps physicians to identify patients requiring immediate treatment. Women with osteopenia, for example, may need urgent intervention if their FRAX score is high. Traditional x-rays are good at picking up fractures, but may not detect osteoporosis until it has become advanced, or 30 percent of bone mass is already lost. Thus, early and accurate diagnosis is the key to preventing irreversible damage and disability that may arise from fractures. Signs and symptoms Osteoporosis has no signs or symptoms and patients may not be aware they have it until they suffer a painful fracture. Only one third of vertebral fractures come to medical attention, where patients typically present with acute back pain, reduction in height and curving of the spine or kyphosis (hunch back appearance or dowagers hump) due to vertebral collapse which is often seen in older women.

Osteoporosis, as is widely known, affects predominantly women, but may affect elderly men as well.

Clinical Guidelines GPs can refer to various guidelines on osteoporosis available at the International Osteoporosis Foundation website. Each country China, Malaysia, Philippines and Thailand has its own guidelines as the prevalence of osteoporosis, diagnosis and treatment of fractures may differ for each country. In Singapore, we have the Osteoporosis Clinical Practice Guidelines which we released in 2009, an updated version of which will be available in 2014. The Singapore guidelines recommend lifestyle measures such as increase intake of calcium, vitamin D and exercise 2-3 times a week particularly resistance and weight-bearing types to increase bone strength and posture stability. Treatment options The goal of treatment in osteoporosis is to improve bone health and prevent fractures. Aside from lifestyle changes, it also helps to reduce falls as it means fewer fractures.

41

July 2012

In Practice
When to refer Very often, the condition is not thought of. Patients who seek consultation for chest symptoms may have compression fractures, but very often, no further action is taken. The vast majority of osteoporosis patients should be managed by GPs, just like hypertension. In case of doubt, use the OSTA test. Then, decide which patient should undergo BMD testing. If the BMD result is abnormal, use the FRAX test. Young patients with fractures who may have endocrine problems and those who do not respond well to treatment should be referred to specialists. Osteopenic patients may also need referral if GPs are unsure whether treatment should be started. Conclusion Osteoporosis is a common, devastating condition that can be treated and prevented. Patients at risk of a first fracture and those with previous fractures need more than lifestyle changes. They need evaluation and specific medication. Once therapy has started, compliance is the key to preventing fractures. Osteoporotic fractures can lead to posture changes, muscle weakness, loss of height; and deformity of the spine. They can also cause chronic pain, disability, loss of independence and premature death. The earlier we treat, the more patients are saved from this debilitating disease.

There is no single drug for all patients. Estrogen replacement can slow bone loss in newly menopausal women. For younger patients (early 60s), there is a wide choice of treatment regimen. Selective estrogen receptor modulators (SERMs), raloxifene, for example, may prevent spine fractures. Biphosphonates (alendronate, risedronate, zoledronate) may be good at preventing both spine and hip fractures in the elderly; however caution is needed in patients with gastroesophageal reflux and kidney problems. Injection with prolia (a RANK ligand inhibitor) may reduce osteoporotic spine and hip fractures and is safe in patients with renal impairment. Some drugs such as teriparetide are bone-forming agents and strontium ranelate has a dual mode of action. Aside from proof of efficacy, the ideal drug should suit a patients fracture type, is convenient to take, is not costly and with fewer side effects. BMD testing can be done every year to monitor treatment response. I would only use bone turnover markers, for example urinary or serum collagen type 1 cross-linked C-telopeptide (CTX), to predict the degree of bone loss without therapeutic intervention and identify which patients to treat, particularly those with osteopenia. One in five patients with an incident vertebral fracture will have another fracture within a year. Thus it is important that vertebral fractures are detected early and treatment is started.

42
July

July 2012

Calendar
European Society of Cardiology Congress 2012 25/8/2012 to 29/8/2012 Location: Munich, Germany Info: European Society of Cardiology Tel: (33) 4 9294 7600 Fax : (33) 4 9294 7601 E-Mail: ascoregistration@jspargo.com Website: www.escardio.org/congresses/esc-2012

38th Annual Meeting of Society of Pediatric Dermatology 11/7/2012 to 14/7/2012 Location: California, US Info: Society for Pediatric Dermatology Tel: (317) 202-0224 Fax: (317) 205-9481 Email: spd@hp-assoc.com Website: www.pedsderm.net 30th International Congress of Psychology 22/7/2012 to 27/7/2012 Location: Cape Town, South Africa Tel: (27) 11 486 3322 Fax : (27) 11 486 3266 E-Mail: info@icp2012.com Website: www.icp2012.com

Upcoming
European Respiratory Society Annual Congress 1/9/2012 to 5/9/2012 Location: Vienna, Austria Info: European Respiratory Society Tel: (41) 21 213 01 01 Fax: (41) 21 213 01 00 E-Mail: ers2012groups@kit-group.org Website: www.erscongress2012.org/ 14th Congress of the International Society for Peritoneal Dialysis 9/9/2012 to 12/9/2012 Location: Kuala Lumpur, Malaysia Info: International Society for Peritoneal Dialysis Tel: (603) 2162 0566 Fax : (603) 2161 6560 E-Mail: ispd2012@console.com.my Website: www.ispd2012.org.my Hospital Management Asia 2012 13/9/2012 to 14/9/2012 Location: Hanoi, Vietnam Info: Ms. Sheila Pepito Tel: (632) 846 8339 Email: sheilapepito@exedraevents.com Website: hospitalmanagementasia.com 15th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2012) 3/10/2012 to 6/10/2012 Location: Florence, Italy Tel: (41) 22 908 0488 Fax: (41) 22 732 2850 Email: esid@kenes.com Website: www.kenes.com/esid

Healthcare in China 2012 24/7/2012 Location: Beijing, China Info: Economist Conferences Tel: (852) 2585 3312 Email: conferencesasia@economist.com Website: http://www.economistconferences.asia/event/ HCCN
17th World Congress on Heart Disease 2012 27/7/2012 to 30/7/2012 Location: Toronto, Ontario, Canada Info: International Academy of Cardiology Tel: (1) 310 657 8777 Fax: (1) 310 659 4781 E-Mail: Klimedco@ucla.edu Website: www.cardiologyonline.com

August
11th Asian Congress of Urology of The Urological Association of Asia 22/8/2012 to 26/8/2012 Location: Pattaya, Thailand Info: 11th ACU Local Organiser Tel: (662) 287 3942 to 3 Fax: (662) 677 5868 Email: secretariat@11thacu2012.org Website: http://www.11thacu2012.org/

43

July 2012

Calendar

42nd Annual Meeting of the International Continence Society 15/10/2012 to 19/10/2012 Location: Beijing, China Tel: (41) 22 908 0488 Fax: (41) 22 906 9140 Email: ics@kenes.com Website: www.kenes.com/ics National Diagnostic Imaging Symposium 2/12/2012 to 6/12/2012 Location: Orlando, Florida, US Info: World Class CME Tel: (980) 819 5095 Email: office@worldclaswscme.com Website: www.cvent.com/events/national-diagnosticimaging-symposium-2012/event-summary-d9ca7715293 5404ebf0404a0898e13e9.aspx Asian Pacific Digestive Week 2012 5/12/2012 to 8/12/2012 Location: Bangkok, Thailand Tel: (66) 2 748 7881 ext. 111 Fax: (66) 2 748 7880 E-mail: secretariat@apdw2012.org Website: www.apdw2012.org World Allergy Organization International Scientific Conference (WISC 2012) 6/12/2012 to 9/12/2012 Location: Hyderabad, India Info: World Allergy Organization Tel: (1) 414 276 1791 Fax: (1) 414 276 3349 E-mail: WISC@worldallergy.org Website: www.worldallergy.org

44

July 2012

After Hours

Chengdu Land of Tea


,
hengdu is truly a place of stark contrasts and contradictions. At one end of the spectrum are large modern buildings and tall elevated highways looming over the city; at the other, you have the old weathered historical buildings dating back centuries and narrow pedestrian walkways. You have Starbucks outlets at every corner and quaint little tea houses dotting the sidewalks. There is a big tea-drinking culture in Chengdu, with many types of green teas grown locally. People sip tea on the sidewalks, people-watching and whiling away the time. There is an unusual level of coziness among the people at the teahouses, which is in sharp contrast to the hustle and bustle around them. The tea culture dates back to the Western Han period from 206 BC and 220 AD, when both the tea trade and tea culture were thriving in Sichuan province, with Chengdu as the starting point of the Southern Silk Road.

Tao& Pandas

Chengdu epitomizes todays China modern, yet historical and quaint. Leonard Yap writes.

About an hours drive (without trafc) and 70 km out of Chengdu lies Mount Qingcheng. Among the most important centers of Taoism in China, it is situated on the outskirts of Dujiangyan City and connected to downtown Chengdu by a modern expressway.

45

July 2012

After Hours
boo groves that mimic the animals native habitat. It is very entertaining to watch pandas going through their daily routine, which includes eating bamboo, taking a nap and playing (for the young ones). One can only feel a hint of envy at the life of the panda, devoid of the complications of human life. Chengdu is certainly a place of surprises and contrasts, where one can get away and yet not be too far away from the conveniences of modern life.

With its peak 1,260 m above sea level, Mount Qingcheng is cool and green all year round, and surrounded by hills and waterways. Laojun Temple and Qingcheng Celestial Hall top its peak and is made easily accessible via cable car. Cable cars glide up through the green forest, providing a breathtaking view of the surrounding mountains. For the adventurous, the climb to the summit is a spirited trek sprinkled with spectacular views and little temples dotting the path. Taoism is a fundamentally Chinese philosophy and religious tradition that emphasizes living in harmony with the Tao, which can be translated as the way or path. Its sacred text, the Tao Te Ching, opens with this poetic line, The Tao that can be named is not the absolute Tao, pointing to a spiritual force that is ultimately beyond our grasp. Taoism emphasizes wu wei (action through inaction), simplicity, spontaneity and harmony between the individual and the cosmos. No trip to Chengdu is complete without a visit to the Giant Panda Research Base. It has a huge breeding and research base for giant and red pandas, and attracts scores of visitors from all over the world. Covering an area of 106 hectares, the research base is filled with bam-

46

July 2012

Humor

Take it easy!

What a pleasant surprise for a change. With all the hypochondriacs coming here, its nice to see someone whos actually sick!

Remember the pills you prescribed to boost my self-confidence? Well, they worked, I just robbed the bank across the street!

We are gonna have to open you up again. My colleague cant find his wedding ring!

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