April 2012

www.medicaltribune.com

Bone screening recommended for heart failure patients

PHILIPPINE FOCUS
Glaucoma Society fights elusive eye disease

FORUM
Diagnostics for the developing world

CONFERENCE
Psoriasis studies show link with stress

CONFERENCE
Protease inhibitors improve outlook in Hep C

NEWS
Contaminated TCM products cause liver damage

IN PRACTICE
Management of endometriosis

April 2012

Bone screening recommended for heart failure patients

Rajesh Kumar esearchers are recommending that patients with heart failure be aggressively screened for osteoporosis and bone fractures. In their study, which analyzed data from 45,509 adult subjects undergoing bone mineral density (BMD) testing over a 10-year period, the presence of heart failure was associated with a 30 percent increase in major fractures independent of traditional risk factors and BMD. Our study demonstrates for the first time that heart failure and thinning of bones go hand in hand, said lead author Dr. Sumit Majumdar of the University of Alberta in Edmonton, Canada. The findings are relevant for Asians, particularly for Chinese and Japanese populations in which rates of osteoporosis and fracture are higher than those seen in other ethnic groups, said the researchers. Of those included in the analysis, 1,841 (4 percent) had recent-onset heart failure. Subjects with heart failure were significantly older (74 vs 66 years), had more previous fractures (21 percent vs 13 percent), and lower total hip BMD than those without heart failure (T-score -1.3 vs -0.9). [JCEM 2012; 11:3055-R2] Over an initial 5-year observation period, 2,703 fractures were reported. Overall, 10 percent of heart failure subjects had major fractures compared with 5 percent of those without (unadjusted hazard ratio [HR] 2.45, 95% CI 2.11-2.85). Adjustment for osteoporosis risk factors, comorbidities, and medications weakened but did not eliminate this

A large survey of more than 45,000 adults showed that heart failure was associated with a 30 percent raised risk of major bone fractures.

association (HR 1.33, 95% CI 1.11-1.60) nor did further adjustment for total hip BMD (HR 1.28, 95%CI 1.06-1.53). Osteoporosis and heart failure are common, chronic and costly conditions that share common etiologic factors such as older age, postmenopausal status and diabetes. Previous studies have suggested that heart failure may predispose a patient to fractures not only because it increases incidence of falling, but because both heart failure itself and its medical treatments can lead to loss of bone mass. Understanding the mechanism between heart failure and osteoporosis might lead to new treatments for both conditions Heart failure should be treated as a stronger risk factor for fracture, just as the classic risk factors such as prior fracture and family history. Part of screening for osteoporosis should involve looking at chest X-rays of patients with heart failure, said Majumdar. Heart failure patients get a lot of X-rays and they often incidentally show many fractures of the spine that would automatically provide an indication of severe osteoporosis and need for treatment.

Change your patients view of the world.

For patients in need of greater IOP reduction after PG monotherapy1

Bimatoprost/timolol maleate (Ganfort) provides a stronger IOP efcacy among FDCs1
Superior IOP control vs. latanoprost/timolol xed combination (LTFC)1
Multicentre, randomised controlled study: GANFORTTM vs LTFC1
IOP-lowering from baseline treatment at 3 months
Post-latanoprost (n=40)
0

Mean diurnal IOP was sign cantly lower in the GANFORT group than the LTFC group after switching from latanoprost monotherapy (p<0.001)1
Adapted from Centofanti et al, 2010. Ef cacy of the xed combinations of bimatoprost or latanoprost plus timolol in patients uncontrolled with protaglandin monotheraphy. 55% and 40% of patients within the GANFORT and LTFC groups respectively had been previously treated with latanoprost 0.005% monotherapy. A multicentre, randomised, investigator-masked, clinical study (n=82). Subgroup analysis of patients on bimatoprost, latanoprost or travoprost baselin monotherapy.

IOP reduction (%)

-7.5 -15 -22.5 -30

13% 24 %
Additional

11%

IOP reduction

p<0.001

GANFORTTM

LTFC

Ref: 1. Centofanti M et al. In uence of baseline treatment on the ef cacy of prostaglandin analogues xed combinations. Poster presented at EGS, September 2010, Madrid, Spain.

Full prescribing information available at the Allergan Hospitality Area.

Prepared: February 2012 ASIA/0067/2011

Unit 2602, Jollibee Plaza Condominium, F. Ortigas Jr. Road (formerly Emerald Ave.) Ortigas Center, 1605 Pasig City, Philippines Telephone: (+632) 470 2286 Fax: (+632) 470 2284

April 2012

Forum

Diagnostics for the developing world

Based on a lecture by Professor Jon Cooper, chair of bioengineering at the University of Glasgow in Scotland, UK, organized by the British High Commission in Singapore recently under the auspices of the UK-Singapore Partners-in-Science program. eveloping world diagnostics is an exciting new area. There is obviously the humanitarian aspect of it in terms of doing better for the world. But it also has some very challenging engineering aspects. In low income countries, 40 percent of people die before the age of 14, whereas in high income ones, 70 percent will survive beyond the age of 70. Most preventable deaths in poor countries occur due to five major diseases: tuberculosis, malaria, pneumonia, rotavirus and HIV. These diseases are responsible for 7.5 million worldwide deaths annually. At the University of Glasgow, we are working on the development of quick and cheap diagnostic tests, not only for the major diseases such as malaria and tuberculosis, but also for many of the so called neglected diseases lymphatic filariasis, trachoma, leishmaniasis, bilharzias (schistosomiasis), sleeping sickness, river blindness, Chagas disease, leprosy and hookworm disease that massively impact the lives of millions. Several global health organizations, along with the UK and US governments, the Bill and Melinda Gates Foundation, and some pharmaceutical companies, recently pledged to combat 10 such neglected tropical diseases over the next decade. They aim to eliminate these diseases through a dramatic increase in drugs and treatment programs in the affected countries. I think low cost diagnostic technologies will also

play a key role in this initiative. Technologies that are currently available in the developing world tend to be fairly simple. Malaria tests, for example, typically involve a blood smear, a stain, and a microscope to look for the plasmodium within the red blood cell. To diagnose sleeping sickness, the demands for detection are acute because of a very low level of parasitemia (perhaps less than one parasite per 100 million blood cells). The diagnostic test needs to be able to detect it, and thats quite demanding. Currently, countries in East and SubSarharan Africa (where sleeping sickness is a problem) have a basic chromatographic exchange column that is used to selectively concentrate the parasites before they are observed under a microscope. That might sound like a very successful technique and it

April 2012

Forum
Surface acoustic wave technology is common in mobile phones. In diagnostics, when you put fluid in the path of those acoustic waves, the interface between the chip, the air and the liquids creates the conditions necessary to separate the sample into its different components for diagnosis. For malaria, we take a blood sample, perform a lysis and use PCR amplification and detect the DNA. In 15 minutes, we can run 30 PCR cycles which provides clear signals at 0.07 percent of parasitemia (equivalent of 10 parasites in a finger prick of blood). There is possibility of using this test either for testing for drug resistant malaria (an emerging problem in northern Thailand) or for multiplexed analysis for malaria, tuberculosis and pneumonia on the same chip. It can also check whether the parasite is resistant to drugs. In dielectrophoresis, particles including cells become polarized within electric fields and we are looking at how we can induce these electric fields optically using a very low power technique. That essentially works on the basic principle that manipulation of electric charges gives rise to a force. The cells move within the electric field based on the magnitude of the force being exerted and result in blood moving in one direction and trypanosomes in another. We then use a simple algorithm to detect the enriched parasites in the sample. The challenge for us is testing and delivering these assays at a low cost. Demonstrating that we can now implement technologically advanced assays into very low cost formats, such as those being developed in paper based Lab-on-a-chip is perhaps the most significant engineering challenge we face.

works pretty well. But the columns are made locally and their availability is sporadic. The technological challenges for developing diagnostics for sleeping sickness are also manifold. The tests need to have a sensitivity of at least 1 to 100 million or should have the capacity to detect a very small number of parasites against a very large background. They should be able to be delivered in places where power and infrastructure is non-existent and they should be very inexpensive. The tests should also work under severe ambient conditions, should be easy to use, and be able to handle blood, urine or saliva samples. The requirement is not just to detect the infection. Due to growing problem of drug resistance, the tests need to be able to see if the bacteria or parasite will respond to commonly used drugs, so we know which drug to give to patients to treat them successfully. These latter assays require the testing of DNA using a nucleic acid test. Several new technologies are already under development involving the use of mobile phones as microscopes and ultra low-cost amenable paper microfluidicsbased tests. At the University of Glasgow, we are also interested in the use of mobile phones in diagnostics. In Africa, there are half a billion mobile phones from the latest 3G ones to those that are 10 to 15 years old with basic functions. All of them have a battery. We see them more as a source of rechargeable power supply for very low powered diagnostic tests. For diagnostic tests for malaria, sleeping sickness and tuberculosis, we are looking at the use of acoustics and dielectrophoresis for separation and sensing.

April 2012

News

Contaminated TCM products cause liver damage

Radha Chitale

ontaminants in traditional Chinese medicines (TCM) can cause serious, sometimes fatal, liver failure, according to research presented at the 22nd Conference of the Asian Pacific Association for the Study of the Liver (APASL) held in Taipei recently. A recent survey of 26 patients admitted to National University Hospital (NUH) Singapore with acute liver failure found that 11 (42.3 percent) of the cases were associated with the use of TCM products. Four of these patients died. Drug-induced liver injury has a different etiology and severity profile in Asia compared with the West and TCMs were the most commonly implicated drugs in our series, said lead researcher Dr. Lim Seng Gee, chief of gastroenterology at NUH. Lim added that the results were unique to Asia, where TCMs are widely available, and that data on herbal medicines are under-reported or poorly reported in general. Previous evaluations of TCM medications which may have been ingested by patients admitted to NUH with druginduced liver injury liver showed that up to 30 percent were adulterated with pharmacologic agents such as corticosteroids, beberine, metformin, phenylbutazone, paracetamol and amidopyrine. Lim pointed out that a natural herb is not necessarily safe or effective, and that while it may not be classified as a drug it can still have a pharmacologic

Some TCM products are contaminated with pharmacologic ingredients which can cause liver toxicity.

effect that can be toxic. In order to reduce the risk of [liver injury], we should discuss [TCM] use in individual patients, recommend nonuse or safe use of reputable products to reduce dose escalation, caution against drug-drug interactions, and monitor patients with hepatitis, he said. The risk of herbal hepatotoxicity and adverse events of herbs seems to outweigh the benefits.

SYMPOSIUM HIGHILGHTS BULLETIN

At a recent training workshop for dental leaders held in Manila, Dr Fritz Ley discussed the growing burden of periodontal infection in the Philippines and around the world. He enumerated current best practices in preventing and treating gingivitis and periodontitis, highlighting the benefits of medicinal toothpaste (Parodontax , GlaxoSmithKline) in reducing plaque formation and gum bleeding in patients at risk of developing irreversible periodontal disease.

Contribution of natural ingredients to oral hygiene: Parodontax for strong gums and life-long healthy teeth
Dr Fritz Ley General Manager Bonapharm GmbH and Dentifritz Consulting Dernau, Germany

medicinal plants that have long been known to exert beneficial effects on periodontal disease (Table). Table. Medicinal plants used in the treatment and prevention of periodontal disease Peppermint (Mentha piperita) antibacterial benefits in inflammatory conditions freshens breath and relieves pain Sage (Salvia officinalis) antibacterial tissue-strengthening deodorant remedy for inflammatory conditions of the mouth and pharynx Coneflower (Echinacea purpurea) strengthens the natural defense of the body proven value in chronic conditions of the mouth and impaired healing Ratanhia (Krameria triandra) astringent effect on gums proven benefit in the treatment of inflammatory conditions of the mouth and pharynx Myrrh (Commiphora molmol) strengthens tissues arrests bleeding especially in patients with inflammatory conditions of the mouth and pharynx Chamomile (Matricaria recutita) anti-inflammatory and antibacterial effects promotes wound healing employed for inflammatory conditions of the gums

Figure 1. Zone of inhibition against Actinomyces viscosus associated with gingivitis3

18 16 14 12

17 15
PARODONTAX PERIDEX (CHX) VIADENT LISTERINE WATER

eriodontal disease is a leading cause of tooth loss worldwide. The usual etiology is a persistent infection that can spread rapidly throughout the periodontium. This is composed of the alveolar bone, cementum, gingival and periodontal ligament. It is considered the most common form of chronic bacterial infection in adults. Based on estimates from the National Monitoring and Epidemiological Dental Survey (NMEDS), its prevalence in the Philippines is increasing, with up to 74% of 12-year-old children being diagnosed with gingivitis in 2006.1 This is in contrast with the prevalence of dental caries which has remained over 90% in the last decade. Without early corrective treatment, gingival problems in childhood appear to increase the risk of developing irreversible periodontal disease during adolescence and adulthood. Similar outcomes can be observed in developed and less developed countries, as was demonstrated in a recent epidemiological study conducted in Switzerland. Among 4,500 subjects 20 years of age and above, 7% of whom were edentulous and approximately 80% of whom had gingivitis, 60% to 84% were at risk for periodontitis, 15% to 33% had moderate periodontitis, and 4% to 7% were diagnosed with advanced periodontitis. Other risk factors that have been identified include the following: Smoking Hormonal changes in women Diabetes Stress Medications Illnesses Genetic susceptibility To address the problem in the Philippines, the National Objectives for Health aimed to reduce the prevalence of periodontal disease to 60% from a baseline of approximately 78% between 2005 and 2010.2 Modern dental care has made this a realistic target, particularly with increasing recognition of the role of medicinal toothpaste as both a therapeutic and preventive agent. The role of biofilm The bacteria associated with periodontal disease reside within biofilms above and below the gingival margin. Biofilms create a self-protective matrix shield by cross-feeding and cross communicating in large numbers and rapidly multiplying. Loosely attached and unattached bacteria found at the biofilm surface have direct contact with the epithelium of the gingival tissue. Biofilms release a variety of biologically active inflammatory products which cause gingival inflammation and can enter the bloodstream, resulting in bacteremia. Research suggests that periodontal bacteremia may lead to: Heart disease, stroke, and/or diabetes Increased risk of delivering a preterm, low birth-weight baby Increased health risk for people with diabetes, respiratory disease or osteoporosis Prevention and treatment of periodontal disease Conventional methods for treating gingivitis and preventing periodontitis include professional cleaning, improving personal oral hygiene, brushing, flossing, rinsing and smoking abstinence. In advanced disease, emphasis is placed on controlling the infection through scaling and root planing, local and systemic medications, and surgery. For practical reasons, toothpaste has become an integral part of periodontal therapy. Modern toothpaste formulations regularly contain mineral salts such as sodium bicarbonate which possesses significant acid buffering capacity and sodium fluoride which helps prevent cavities. In addition, some products include active components of

mm

10 8 6 4 2 0

7.5

Figure 2. Zone of inhibition against Streptococcus mutans associated with caries3

20 18 16 14 12 10 8 6 4 2 0

19

17

mm

PARODONTAX PERIDEX (CHX) VIADENT LISTERINE WATER

Figure 3. Frequency of gingival bleeding on probing after 4 weeks7

30 25 PARODONTAX PLACEBO

Percent

20 15 10 5 0 BASELINE 4 WEEKS

Parodontax: a giant leap for periodontal care Parodontax is a unique medicinal toothpaste family used for the treatment and prevention of gum disease. The product was developed in 1937 by German dentist Dr Focke and is now commercially available in more than 30 countries. Unlike other toothpaste preparations that are being marketed for the same indication, Parodontax contains 67% sodium bicarbonate and six herbs. It is red in color, has a distinct taste and does not foam like conventional toothpastes. Parodontax is recommended for use two to three times daily, particularly before breakfast and at bedtime. Besides using it with regular brushing, it can also be applied directly on the gingiva using a tray, with contact time optimized by not rinsing. Scientific evidence corroborates the effectiveness of Parodontax in eradicating common oral pathogens responsible for gum disease, with inhibition of Actinomyces viscosus and Streptococcus mutans being demonstrated in at least two test models (Figure 1 and Figure 2). 3 Peppermint and sage oils contained in Parodontax have been found to have both bactericidal and bacteriostatic properties and can kill microorganisms including anaerobic bacteria that cause periodontitis through a targeted mechanism. These volatile oils denature proteins in bacterial cell walls, allowing cell contents to leak out. This ultimately leads to cell death. An additional benefit of Parodontax is its ability to neutralize the acid that attacks teeth and gums, thereby aiding in plaque prevention and reduction.4 It is capable of acting as a buffer, removing acid in the mouth through bicarbonate trapping and formation of carbonic acid which is then broken down into carbon dioxide and water. 5 The carbon dioxide is subsequently released harmlessly from the mouth by exhalation. 3 In a 4-week, single-blind, placebo-controlled study involving 50 healthy adults between the ages of 23 and 28 years, use of a toothpaste containing medicinal herbs significantly reduced the approximal plaque index (API) from 40.8% to 23.9% and the sulcus bleeding index (SBI) from 33.4% to 18.6% in the active treatment group by the end of the study.6 The pH of the total saliva was significantly shifted into the alkaline range by the application of the herbal products, whereas the placebo products had the opposite effect.

The benefits on gingival bleeding were confirmed by another 4-week trial (n=22) investigating the effectiveness of Parodontax dentifrice compared to a control dentifrice. While there was no significant difference between groups at baseline, Parodontax produced a significant decrease (p<0.01) in bleeding on probing (Figure 3) compared both to baseline (p<0.01) and to the control group (p<0.05).7 Furthermore, the number of bleeding sites were significantly reduced in the Parodontax dentifrice group from baseline to study completion (p<0.001). A separate study (n=128) published a year earlier had already shown that bleeding on probing scores could be significantly lowered by Parodontax compared with placebo after 6 months of unsupervised home use.8 Two subsequent studies demonstrated that Parodontax applied over 2 weeks with a tray reduces gingival bleeding by approximately 30%.9,10 Summary Given the rising prevalence of gingivitis and periodontitis, multiple strategies must be employed in order to achieve urgent local and international dental health goals. Among standard therapeutic options, medicinal toothpastes such as Parodontax that contain natural herbal ingredients are both practical and effective in reducing bacterial colonization, plaque formation and gingival bleeding in patients at risk for irreversible periodontal disease.
References 1. Republic of the Philippines Department of Health web site. What are the latest dental problems statistics of the Philippines? http://dohgov.indanet.com/content/what-are-latest-dental-problems-statistics-philippines. Accessed November 25, 2011. 2. Villaverde MC, Beltran MM, David LC, eds. National objectives for health Philippines, 2005-2010. Manila: Department of Health; 2005. 3. Yankell SL, Emling RC. Two month evaluation of Parodontax dentifrice. J Clin Dent 1988;1(Suppl A):A41-43. 4. Guggenheim B, Lutz F, Schmid R. Caries and plaque inhibition in rats by five topically applied dentifrices. Eur J Oral Sci 1997;105:258-263. 5. Ghassemi A, Vorwerk LM, Hooper WJ, Putt MS, Milleman KR. A four-week clinical study to evaluate and compare the effectiveness of a baking soda dentifrice and an antimicrobial dentifrice in reducing plaque. J Clin Dent 2008;19:120-126. 6. Willershausen B, Gruber I, Hamm G. The influence of herbal ingredients on the plaque index and bleeding tendency of the gingiva. J Clin Dent 1991;2:75-78. 7. Saxer U, Jaschouz V, Ley F. The effect of Parodontax dentifrice on gingival bleeding. J Clin Dent 1994;5:63-64. 8. Yankell SL, Emling RC, Perez B. Six-month evaluation of Parodontax dentifrice compared to a placebo dentifrice. J Clin Dent 1993;4:26-30. 9. Ernst CP, Owin K, Willershausen B, Meinert R. Application of an antimicrobial gingivitis prophylaxis with herbal ingredients. ZWR 1996;105:532535. 10. Willershausen B, Owin K, Ernst CP. Clinical investigation on tray application of a gingivitis prophylactic with herbal ingredients, main study. ZWR 1996;105:532-535.

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April 2012

Philippine Focus

Glaucoma Society fights elusive eye disease

Gabriel Angelo Sembrano, RN he Philippine Glaucoma Society (PGS) launched this years World Glaucoma Week on March 7, 2012 at the Makati Shangri-La Hotel with a warning: Dont Let Glaucoma Darken Your Life! PGS is an internationally-recognized leader in providing quality glaucoma care in the Philippines primarily through education and research. Victims of irreversible blindness may not know that they have the disease until it is so late that they have lost a large area of their vision, as in most types of glaucoma, also dubbed as the sneak thief of sight that destroys vision without causing obvious symptoms. Glaucoma occurs when channels that drain eye fluid get blocked and pressure in the eye builds resulting in the loss of vision. Early detection of the disease is crucial to effective management, said Dr. Rainier Covar, PGS research committee member. This event is part of a series of activities organized by the society and the members of the Philippine Academy of Ophthalmology for the month of March. Free eye checkups and awareness forums will take place in 63 private and public health facilities in 25 participating sites nationwide. World Glaucoma Week was established in response to the worldwide concern over the increasing number of people with glaucoma. If these people do not have the condition detected and treated right away, more people, including Filipinos, are at risk of going blind from this disease, said founding PGS president Dr. Mario Aquino.

Members of PGS Dr. Mario Aquino, Dr. Rainier Covar, Dr. Ma. Imelda Yap-Veloso and Dr. Jose Ma. Martinez during the press conference

In the Philippine National Survey of blindness, glaucoma is the leading cause of bilateral blindness in the country. Glaucoma is thought to be the primary reason for preventable loss of vision and in fact, statistics show that over 60.5 million people around the world suffer from the disease, of which 8.5 million of them are already blind in both eyes, PGS president Dr. Ma. Imelda Yap-Veloso explained. The Philippine Glaucoma Foundation cites the following conditions as risk factors to Glaucoma: elevated eye pressure, previous eye injury, chronic steroid use, diabetes mellitus, age of at least 45 years, family history of glaucoma, and Chinese ancestry. People with these issues must seek Glaucoma screening from an ophthalmologist. Blindness caused by glaucoma, unlike cataract, is permanent and cannot be cured; however, it may be controlled upon early discovery. Hence, lifelong monitoring and treatment through eye-drops, laser, or surgery depending on the type and stage of glaucoma are necessary.

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April 2012

Philippine Focus

Worlds only flying eye hospital lands in Iloilo

Gabriel Angelo Sembrano, RN he Flying Eye Hospital, ORBIS Internationals flagship a converted DC-10 aircraft and the worlds only ophthalmic surgical and training hospital with wings made possible by FedEx Corporation landed in Iloilo, Philippines for a 3-week medical program last Ferbruary. The activity targeted both local eye care professionals in the Western Visayas Region and patients identified by the Western Visayas Medical Center who were suffering from visual impairment. The ORBIS medical team conducted an intensive skills exchange program with local eye care professionals. The mission extended to a hospital-based program in Bacolod City, in partnership with the Corazon Locsin Montelibano Memorial Regional Hospital. A survey conducted in the Philippines by the Department of Health in 1995 showed that 0.7% of Filipinos are bilaterally blind. Among the top leading causes found in this survey were cataract, glaucoma and uncorrected aphakia. Treatments for these are simple and effective but are not readily available for those who are poor and living in rural areas. ORBIS is excited to conduct its first Flying Eye Hospital program of 2012 in the Western Visayas Region of the Philippines, said David Johnson, Flying Eye Hospital director with ORBIS International. This year marks the 30th anniversary of the Flying Eye Hospitals sight-saving program in the Philippines. It is the hospitals 11th time in the country since 1982. For more than 25 years now, FedEX

has been a partner of ORBIS international in delivering services to areas where eye care is far from available. FedEX has been supporting ORBIS in its mission to eliminate avoidable blindness across the world. As the leading aviation sponsor for three decades, FedEx continues to support ORBISs sight-saving programs around the world, through our extensive global network and aviation expertise, explained Rhicke Jennings, FedEx Express managing director for the Philippines and Indonesia. In 2011, FedEX renewed its commitment by a $5.5 million for 5-years grant. The company has also donated an MD-10 cargo aircraft and was converted into the third-generation, state-of-the-art Flying Eye Hospital. Together with FedEx and our local partners, we will address the leading and emerging causes of blindness, including cataract, diabetic retinopathy and pediatric eye disease, while we continue to raise awareness of avoidable blindness, David Johnson said.

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April 2012

Philippine Focus

Pharma industry: No more personal gifts for doctors

Dr. Yves St. James Aquino he Pharmaceutical and Healthcare Association of the Philippines (PHAP) is aiming for stricter implementation of expanded code of practice that prohibits bribery among members of the healthcare industry. Pharmaceutical companies have been criticized for using expensive personal gifts and frequent sponsorships given to doctors and other healthcare professionals to promote their products, which consequently drives up the cost of medicines. Developed by the Geneva-based International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), the expanded Code of Practice now includes more specific guiding principles that include clearer distinction between gifts, promotional aids and items of medical use. It also provides guidance on how to implement continuing medical education and how to disclose results of clinical trials. Interactions between the medical community and pharmaceutical industry are crucial to advance medical knowledge and improve public health. In all these interactions, integrity as well as the healthcare and well-being of Filipino patients are our priority, said PHAP executive director Reiner Gloor in a statement. The revised code of practice specifies travel sponsorships, stating that companies can only sponsor travels by physicians if it is for the purpose of medical education that is not available in our country.

The Code also bans company-sponsored entertainment events. Instead, all events must be held in appropriate venues that are conducive to the scientific or educational objectives of the meeting, said the statement. The 44 members of PHAP are expected to comply with the stricter rules to further establish ethical standards in promoting their products. According to the ethics committee of PHAP, sanctions may involve fines, suspension from PHAP or expulsion with public announcement when previous sanctions imposed were disregarded by the violator.

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April 2012

Philippine Focus

TREATMENT FOCUS: Pain management

Opioids as viable option in treating cancer pain

Dr. Adrian Paul J. Rabe ith the growing prevalence of cancer, encounters with cancer-related pain are expected to rise. Dr. Dennis Sacdalan, an expert in medical oncology and affiliated with The Medical City and the University of the Philippines-Philippine General Hospital, reports that the majority of malignancies present with pain, with up to 60% of cancer pain being related to metastatic disease. The pathophysiology of pain in cancer is most commonly through mass effects, causing distension of organ capsules and surrounding organ tissue, as well as compression of nerve fibers that transmit pain. The inexorable process of malignant growth produces both acute and chronic pain which severely limit the quality of life of many patients. Two of the primary resources for clinicians in the management of cancer pain are the World Health Organization (WHO) analgesic ladder and the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology: adult cancer pain. The WHO analgesic ladder recommends the use of opioids as a second-line drug class for relief of mild pain, as well as for pain that is moderate to severe. In his oncologic practice, Sacdalan says that he utilizes opioid derivatives such as tramadol for moderate pain and morphine for severe pain. This approach appears applicable and effective in most patients. Despite numerous reviews and growing

clinical experience, opiophobia, or the reluctance to give opioids, remains prevalent in many developing countries. There are three main concerns frequently cited by physicians that prevent them from prescribing opioids. These are the following: 1. Lack of familiarity with opioids (such as dosing, pharmacokinetics and titration), 2. Side effects related to opioids especially in the context of patients who frequently have multiple medications, and 3. Fear of addiction to opioids. Basic pharmacology of opioids Opioids act mainly as an agonist of 3 receptors, mu 1 and 2 receptors (found in the brainstem and medial thalamus), kappa receptors (found in the limbic area and other diencephalic areas, brain stem, spinal cord), and delta receptors (found mainly in the brain). (See table.) The effects of opioids are dose-dependent. Since opioids act mostly on the brain and the spinal tract, they achieve analgesia despite the variety of mechanisms of pain and are hence quite versatile. Aside from analgesia, opioids can cause euphoria or sedation. Codeine, specifically, is known for its cough suppression. Undesirable side effects are respiratory depression, truncal rigidity, nausea and vomiting. It can also cause hypotension in hypovolemic patients, constipation and urinary retention. Some patients may experience histamine release, with consequent flushing, sweating and itching. Many of

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April 2012

Philippine Focus
Delta Analgesia Spinal analgesia Kappa Analgesia, sedation, dyspnea, psychomimetic effects, miosis, respiratory depression, euphoria, dysphoria

TREATMENT FOCUS: Pain management

Opioids and their pharmacologic effects
Receptor Function Mu 1 and 2 Mu 1: analgesia Mu 2: sedation, vomiting, respiratory depression, pruritus, euphora, anorexia, urinary retention, physical dependence Agonists Morphine Codeine Codeine Methadone Antagonists Naloxone Naltrexone Antagonist Antagonist Weak antagonist Weak antagonist Antagonist Antagonist Agonist Weak agonist Agonist Agonist Weak agonist Weak agonist

Adapted from Trescot AM, Datta S, Lee M, and Hansen H. Opioid pharmacology. Pain Physician 2008; 11:S133-S15.

these side effects are avoidable with careful titration of the medication dose and anticipatory care. Many opioids are metabolized in the liver through conjugation and oxidative metabolism and have minor enterohepatic recirculation. Minor metabolism occurs in tissue through esterases. Excretion of these metabolic products is through the kidneys and bile. Available opioid prototypes Morphine is a familiar example of an opioid. In patients who have no opioid exposure in the past, morphine is considered the first drug of choice for cancer pain. It is flexible in that it can be administered through all drug routes. The time to peak effect for intramuscular morphine is 30 to 60 minutes and the duration of action is 3 to 4 hours. Morphine has no ceiling dose, with its limit defined by the presence of intolerable side effects.

Fentanyl is 100 times more potent than morphine. When given intravenously, it has a more rapid onset of action (30 minutes) and short duration of action (1 hour) especially when given in single doses. When used in multiple doses, the duration of action of fentanyl prolongs to ~3 hours. Codeine is available in the Philippines as an oral medication. Its maximum daily dose is 360 mg. As mentioned, this opioid is used as a cough suppressant, but is synergistic with non-steroidal anti-inflammatory drugs (NSAIDs) as a pain medication. It has much lower incidence of euphoria and has a lower addiction potential than morphine. Oxycodone has a rapid onset of action at 10 to 15 minutes. It is two times more potent than morphine orally, but is less potent than morphine parenterally. This medication is used frequently in conjunction with NSAIDs. It has an addictive potential similar to morphine. Tramadol is an atypical opioid very

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April 2012

Philippine Focus
Constipation is the most common opioid-induced complication, thus increasing the role for prevention of this side effect. Opioids are also known to promote histamine release, producing pruritus. Nausea is also a common complication that may be managed expectantly. Despite all of these adverse effects, a key point in management is to first rule out malignancy as the cause rather than automatically pin the blame on opioids. A careful history and physical examination along with a thoughtful diagnostic plan prevents interchanging cancerinduced effects and opioid complications. Opioids in the spectrum of cancer care Pain management is a crucial point to discuss with patients to ensure that treatment expectations are realistic. Non-pharmacologic options may also be explored, such as massage, physical therapy, or even cognitive approaches (eg, distraction training, relaxation training). Tumor control is an important treatment option for cancer pain especially when patient has metastasis or large tumors. Chemotherapy and radiotherapy are thus used as palliative measures to reduce pain. The diagnosis of cancer is life-changing. Even priorities in care are modified to accommodate the peculiarities of cancer care. Instead of first do no harm, the primary goal in cancer care is primum succurrere, or first hasten to help. Quality of life is thus of prime importance in the cancer patient population. As drugs that directly block the pain pathway, opioids should become a valuable part of your weaponry in combating the debilitating effects of cancer.

TREATMENT FOCUS: Pain management

commonly used for non-cancer pain. It has high oral bioavailability especially when given in multiple doses. Its half-life is similar to morphine, and has an equi-analgesic oral dose to oral morphine of 4:1. This means that if a patient is on 5 mg of oral morphine, the same analgesic effect can be achieved with 20 mg of oral tramadol. Advantages of tramadol would be lower incidence of cardiorespiratory depression than morphine, as well as less constipation. Importantly, addiction potential is also low. The incidence of most other side effects (eg, nausea, vomiting) would be similar to morphine. Its maximum daily dose is 400 mg. Opioids as part of your arsenal The main goal of opioid use is pain relief without causing intolerable adverse effects. Route of administration should be selected based on patient preference, and should be the least invasive, easiest and safest. The oral route is thus preferred for chronic pain management. For most patients, pain relief through as needed dosing may be utilized. In patients who experience chronic pain, a referral to a pain specialist (ie, anesthesiologist or a palliative care specialist) is warranted. These specialists perform dose titration and monitoring for a wider range of drugs. In order to prevent abuse and dependence as well as reduce adverse effects, an opioid is replaced with another opioid in equi-analgesic doses, termed opioid rotation. Dose titration to the lowest possible analgesic dose is also performed. Addition of non-opioids is a recommended strategy to wean patients off higher doses of opioids.

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BEYOND THE CLINIC

Perpetual help, from hospital to municipal hall

Dr. James Salisi

n the right drawer of Glan, Sarangani Vice-Mayor Vivien Yaps desk is a stethoscope, a symbol of her love for medicine and a sign that she has not really stopped practicing her first profession. She is one of the few physicians who have taken on a patient with the most complex problems, the Filipino people. Born to a political family in Glan, Sarangani, Dr. Yap as she prefers to be called wanted to be a pediatrician. However, she decided to come home to Glan because of her family. I had to come home for my parents then; my father was the mayor and my mother was the district supervisor. Somebody had to monitor the health of my father so I finally I decided not to go into training and just practice in Glan, she said. She established an out-patient clinic in Glan and called it Perpetual Help Clinic. Her practice immediately picked up because she was one of the few doctors practicing in Glan. After two years she expanded and put up a lying-in clinic. What she earned from this venture she used to help her parents and her siblings. She practiced actively for 14 years until in 2000 when her father passed away, which also marked her first foray into politics. When my father died, walang tatanggap sa posisyon sa pamilya namin, so I became a municipal councilor for eight months, she said. She was appointed by the governor but controversy surrounding

her appointment prevented her from finishing the term. In 2001 she ran for Barangay Captain of Barangay Poblacion and won. Campaigning opened Dr. Yaps eyes to the extreme poverty that prevented her patients from following up. I realized why my poor patients would abscond. They barely have anything to eat and when they spend their money on food they have nothing left for medical care, not even to pay for fare going to the clinic, she said. As her career in politics blossomed she slowly had to let go of her medical practice. While she would still see patients, it was not as frequent and as involved as before. People would consult her about their illnesses more often in her office at the barangay hall or on the street than in her clinic. After her mothers death, Dr. Yap became more involved in public life. She was president of the board of directors of South Cotabato Electric Company II in 2008 while serving simultaneously as the president of the Federation of Associations of Barangay Captains of Sarangani Province, board member of the province and barangay captain. Because of the demands of her duties she gave up her medical practice and closed her clinic. We are trying to let people see for themselves that we can do without graft and corruption. She believes that governance by good example could bring progress and development in her municipality. She advocates for market-driven sustainable

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rewarding profession for Dr. Yap than public office. But she does not see this as a reason to take advantage of her position and be corrupt. She says that she has saved enough from her practice not to be tempted. Her privacy has also suffered and she sees this as one of the greatest sacrifices that she made for politics. Nevertheless, these losses are negligible. Public office is her means of doing her part to contribute to the progress of Glan, to treat the greater illness of her constituents poverty. I love my being a doctor first, second na yung kung anong mararating ko. I am trying my best now to be a good politician, she said.

BEYOND THE CLINIC

development that starts in the barangays, prioritizes social services such as health care, and promotes livelihood programs to help her constituents get out of poverty. Every year she sponsors surgical missions in cooperation with NGOs. Bringing her work ethics as a physician into her office as vice-mayor, Dr. Yap demands professionalism from her staff, writes ordinances and resolutions, and leads the local anti-poverty action plan group. In 2011, Dr. Yap was awarded as the most outstanding Vice-Mayor in the Philippines by the Gawad LVM Information Research Services for her leadership and exemplary performance. Medical practice was more financially

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April 2012

Philippine Focus

BEYOND THE CLINIC

ADVERTORIAL

The need for vitamin supplementation in older adults

ersons within the adult age group, especially those who are aged 50 years and up, are often busy and may be subject to many stresses that can affect their physical and mental health. Poor nutrition, combined with lifestylerelated factors, can increase the probability of chronic non-communicable diseases and premature deaths among Filipino adults.1 Thus, proper nutrition and regular physical activity are recommended for the prevention and control of diseases such as hypertension, diabetes and dyslipidemia. Another cause of concern for older adults is the normal physiological changes brought by aging. Subtle yet irreversible changes occur as early as the fourth or fifth decade of life, with progressive deterioration afterward.2 These changes predispose older adults to increased risk of malnutrition, including mineral and vitamin deficiencies, which are estimated to occur in almost 35% of people over the age of 65.3 Nutritional status is an important factor in the development of various morbid conditions found in the aging adult, including cancer, heart diseases and dementia. Hypertension usually occurs at age 40 years while bad cholesterol levels peak between the ages of 40 and 70 years.4 Several physiologic changes in normal aging includes atrophy of heart muscles, calcification of heart valves, loss of elasticity in artery walls and accumulation of intra-artery deposits. These result in

reduced blood flow, reduced renal and hepatic function, and impaired blood pressure and even cause heart blocks.5 To ensure cardiovascular health and a healthier aging, adults should ensure intake of B vitamins for regulation of plasma homocysteine levels. Beta-carotene, selenium, manganese, zinc and vitamins C and E for antioxidants help control free radical damage. Overall, healthy diet and regular physical activity can decrease the risk of cardiovascular ailments and other non-communicable chronic conditions.
References: 1. FNRI-DOST. Philippine Nutrition FActs and Figures 2008. FNRI, Bicutan, Taguig City, December 2010. 2. Boss, G and Seegmiller, J. The Western Journal of Medicine, 1981;6(135):434:441. 3. Wells, J and Dumbrell A. Clinical Interventions in Aging, 2006;1(1): 67-79. 4. Abille, E. The ABCs of Reducing CVD Risk Among Filipinos. Article accessed from www.fnri.dost.gov.ph last November 9, 2011. 5. Lata, H. Ageing: physiological aspects. JK Science, 2007;(9)3:11.

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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

Information and socio-economic support needed for glaucoma

uring the World Glaucoma Week, which is celebrated in the month of March, the generally silent cause of blindness was put into focus. Most cases of glaucoma are asymptomatic, with the irreversible vision loss starting gradually until it worsens to total blindness. In the Philippines, glaucoma has now been ranked as the leading cause of blindness in both eyes. This is the challenge faced by the Philippine Glaucoma Society, an internationally recognized leader in providing quality glaucoma care in our country, especially when it comes to helping indigent patients. Because, as you know, we treat glaucoma with eye drops in the beginning. Theyre very expensive. One eye drop can cost you about a thousand pesos a month. And you can imagine for a person who doesnt earn even a thousand pesos in a week, thats going to be the problem, said Dr. Ma. Imelda Yap-Veloso, president of the subspecialty society. Besides financial concerns, the society also has to deal with majority of elderly patients who often attribute their vision loss to the natural cause of aging. The society emphasizes that the damage to the nerve is permanent, which is why prevention or control of progression is important. Yap-Veloso, who received her training from the Harvard Medical School affiliate

Dr. Ma. Imelda Yap-Veloso President Philippine Glaucoma Society

Massachusetts Eye and Ear Infirmary in Boston, US, knows the consequences of this condition too well. She shared that her strong family history of the disease is one of the major reasons why she entered the subspecialty. I have an uncle who is practically blind, with just one eye that can see, and its a very limited vision, said Yap-Veloso. She added that her mother and her mothers siblings also have the condition.

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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
I wanted to know what one can do as a doctor to stop or control it at a certain point. Thats actually what attracted me to become a specialist, she said. Yap-Velosos role as the president gives her the opportunity to spearhead campaigns to promote awareness about the disease. One of the programs held at the start of the World Glaucoma Week was the second Philippine Glaucoma Congress. We invited speakers from around the world to give us the latest in glaucoma from their perspective. So they can share it with us and we can share it with the general ophthalmologists; whats the latest and how you can improve your glaucoma care, she said. The term of Yap-Veloso also initiated a research that will gather information on glaucoma cases in the country. She shared that when she goes abroad for speaking conventions and participants ask about local data, our neighboring countries could answer, while we grapple with lack of local information. Because we dont have data that are scientifically gathered and analyzed. Were working on the draft now for that protocol, she said. Presently, Yap-Veloso is a member of the teaching faculty of the Sentro Ophthalmologico Jose Rizal of the Philippine General Hospital, the premier institution that primarily serves indigent patients. It is to the interest of Yap-Veloso to create a more organized system to help patients who need financial support. We have a foundation now that can help patients have surgery, laser. And at least we can give patients medicines donated by drug companies. Trying to get that all in order and making it a very systematic and fair way of distributing is what we have to work on, concluded Yap-Veloso.
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Philippine Focus

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

Interpersonal relationships inspire a whole organization

t doesnt happen overnight. Like others, you have to rise through the ranks, said Dr. Ma. Teresita Gabriel, president of the Philippine Dermatological Society (PDS), regarding her role as the head of the national dermatological association accredited by the Philippine College of Physicians and the Philippine Medical Association. Gabriel realized her passion for leadership early on in her career, being invited to become a training officer in dermatology section of the Research Institute of Tropical Medicine (RITM) right after her specialty training. At present, she heads the section that two years ago has been approved by the institute to become a fullfledged department. She was a board member of the specialty society for eight years, becoming an active member and chair of numerous committees. In 2009, she was elected as the PDS vice president. Gabriels term saw the growth of Philippine dermatology, with the societys more active role in recent and upcoming annual conventions. The 1st National Conference of PDS was held last November, with the theme PDS Gives Back: Service with Compassion. Last February, the Philippines hosted the 20th Regional Conference of Dermatology, which was attended by delegates from Southeast Asian countries Malaysia, Singapore, Thailand and Indonesia, and guest speakers

Dr. Ma. Teresita Gabriel President Philippine Dermatological Society

from Australia, the US and the UK. PDS was also invited to present at the International League of Dermatological Societies Summit to be held in Berlin, Germany this coming June. After a decade of membership, this is the first time that the Philippines will have the opportunity to present to the international league. Thats something that we should be proud of. ... We will now be known by the rest of the world because we will be there to present the society profile and our awareness campaigns, our projects, shared Gabriel. One of the projects is called Sagip Balat

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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
(Save the Skin) Program. As with World Health Organizations disease focus every month, the Sagip Balat Program will have PDS focus on one dermatological condition per month. The disease will be the basis of that months awareness campaigns, which involves lay seminars, outreach activities and medical missions. And with the growing concern about overuse of cosmetology procedures and products, PDS also launched the PDS Skin Safety Campaign to encourage patients to seek proper consult with legitimate dermatologists. So that we are able to protect the public from incompetent dermatologist claiming to be dermatologists, said Gabriel. She also emphasized that members of PDS, based on the societys ethical guidelines, are not allowed to advertise. Thats one clue that the one whos advertising is not a PDS dermatologist. Gabriel admitted that some would ask if to be a dermatologist you have to be a doctor. She clarified that to be a dermatologist under the PDS, one has to be medical doctor. Then you have to have three years of rigid training in 11 accredited PDS institutions. No mentorship. It has to be an institution. Then after three years, you take the specialty board of dermatology. After that, you can still go into subspecialty training like dermatopathology, phototherapy, dermatological surgery, added Gabriel. To maintain credible specialists, Gabriel also set up the L.E.A.P. or LIFE (Leadership, Integrity, Faith and Excellence) Enhancement Action Program. The program is aimed at providing relevant topics for the members of PDS to make them more well-rounded, ethical, articulate and up-to-date. We veer away from the usual dermatological topics. We do topics like integration and harmony, religion, leadership. The last one we discussed was assertive communication, she said. This program represents Gabriels attitude on how to take on a leadership role, and that is to emphasize the importance of communication and interpersonal relationships. If youve handled a lot of residents, a lot of people, thats interpersonal relationship. Its difficult to be in a high position without interpersonal relations. It cannot be just academic. You have to have some form of assertive communication. Because when you are dealing with people, it would be nice to see both sides. You have to be broad-minded, she explained. Mentorship, according to Gabriel, is a fulfilling duty for her as a leader. You have to be soft. When you give praises, it should be in front of a lot of people. When you have some [critical] comments, you can discuss that when its just the two of you. With all the implemented, ongoing and future projects of the society, Gabriel insists that success is all about teamwork. It cannot be just because of the president. It has to be a collective effort of the rest, not just the board, not just the council of advisers. I think, the general membership has a big support for all the activities; that is why we have a successful society, said Gabriel.

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CASE STUDY

A case of Familial Parkinsonism in a male from Panay Island, Philippines

parkinsonism in an elder brother and in three maternal uncles who live in Iloilo, Philippines. There is no similar history in his paternal relatives. There is no history of exposure to environmental toxins. Physical and neurologic examination revealed masked facies and bradykinesia. He had poor arm swing, a stooped posture, and shuffling gait. There was occasional blepharospasm and spontaneous dystonic dorsiflexion of his big toe. The rest of the examination was normal. Caudate atrophy was seen on MRI. Discussion X-linked Dystonia Parkinsonism (XDP, DYT3) is an adult-onset, sex-linked neurodegenerative movement disorder that manifests with features of both dystonia and parkinsonism. The condition presents itself initially as a focal dystonia, with spread and generalization in 2 to 5 years. Subsequently, there is diminution of the dystonic movements and parkinsonism predominates beyond the 10th year of illness. The condition was first described in Advances of Neurology by Lee et al. in 1976.1 The article on Torsion Dystonia in Panay Island, Philippines described 28 Filipino adult males with dystonia, 23 of whom came from the island of Panay. The typical picture is an adult male with severe, generalized, continuous contorting movements and frequent use of sensory tricks in the early years of the disease. While

Dr. Aloysius Domingo XDP Study Group, Philippine Childrens Medical Center

Case background A 36-year old Filipino male consulted for shuffling gait. On history, the patient had motor slowing and dysarthria since two years prior to consult. There were no reported tremors. The patient had previously consulted with another physician for blepharospasm, involuntary pursing of the lips, and involuntary neck extension 5 years ago. Recently, he has also noticed involuntary dorsiflexion of his big toe. Investigation of family history revealed

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CASE STUDY
most patients are seen in this phase of obvious and disfiguring generalized dystonia, the disease usually initially manifests with less conspicuous focal or segmental dystonia in the lower extremities such as forced dorsiflexion of the big toe, fanning of the toes and foot inversion; or in the craniofacial areas, such as blepharospasm, facial twitching and mouth pursing. Regardless of the initial site of involvement, the dystonia generalizes and becomes severe, with prominent involvement of the axial musculature in two to five years. Involuntary jaw opening and closing, neck retroflexion and torsion and alternating truncal flexion and extension are frequently seen. At this point, the spasms are so severe as to prevent normal gait and even activities of daily living. There is then plateauing in the severity of dystonia and as the patient approaches his 10th year of illness, bradykinesia and parkinsonism set in. In the majority of cases, however, the dystonic movements only diminish but continue on as postural dystonia, so that the usual final outcome is that of combined dystonia and parkinsonism in a single patient. Patients with parkinsonism as the initial manifestation have also been described.2 The condition is endemic to Panay Island, Philippines. In a review of 505 registered cases with the XDP Study Group from 1975-2010, the overall national prevalence rate is 0.31/100,000 population, but it is 5.74/100,000 in Panay. Among the provinces in Panay Island, Capiz has the highest rate at 23.66 cases/100,000 population, or one in about 4,000 males. In Iloilo, the prevalence is 1.33/100,000 persons.

Positive family history is found in 92 percent of cases, and the male to female ratio is 100:1.3 Neuroimaging findings reveal hyperintense putaminal rims in the dystonic, combined, and parkinsonian stages of the disease and varying degrees of caudate and putaminal atrophy in the combined and parkinsonian stages. The neuroimaging findings in these late stages are similar to juvenile Huntingtons Disease. Pathological studies of brains of persons with XDP have revealed a mosaic appearance of the caudate and putamen. Using immunostaining methods, previous studies have described patchy neuronal loss in the caudate and putamen corresponding to loss of the striosome component with preservation of the matrix component in the dystonic phase of the illness. The striatum in the parkinsonian phase showed loss of both striosome and matrix components.4 Sex-linked transmission was inferred when the condition was first described

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XDP Study Group reported efficacy of levodopa-carbidopa in reducing the BFM and UPDRS scores of subjects with XDP between first and last trial visits (Jamora et al., unpublished). Five cases of XDP have also underwent deep brain stimulation (DBS) in the Philippines with encouraging results. DBS in one young patient with XDP showed an immediate 63 percent improvement in BFM score post-DBS, and an improvement of 88 percent in BFM score and 57 percent in UPDRS score one year post-surgery; these seem to be the best obtained outcomes for pallidal DBS in XDP.7 There was significant improvement of gait, resolution of limb, orofacial and neck dystonias, and a subsequent return of the patient to independence in activities of daily living and even employment. X-linked Dystonia Parkinsonism is an unfortunate heredodegenerative illness affecting males from Panay Island. However, current efforts to determine the XDP-specific gene and the diseases response to oral pharmacotherapy and deep brain surgery should give our patients reasonable hope.
References: 1.Lee L, Pascasio F, Fuentes F, Viterbo G. Torsion dystonia in Panay, Philippines. Advances in Neurology. 1976;14:137-151. 2. Lee L, Maranon E, Demaisip C, Peralta O, Borres-Icasiano R, Arancillo J, Rivera C, Munoz E, Tan K, Reyes MT. The natural history of sex-linked recessive dystonia parkinsonism of Panay, Philippines. Parkinsonism and Relat Disord. 2002;9:29-38. 3. Lee L, Rivera C, Teleg RA, Dantes MB, Pasco PM, Jamora R, Arancillo J, Villareal-Jordan RF, Rosales RL, Demaisip C, Maranon E, Peralta O, Borres R, Tolentino C, Monding M, Sarcia S. The unique phenomenology of sexlinked dystonia parkinsonism (XDP, DYT3, Lubag). Int J Neurosci. 2011;121 Suppl 1:3-11. 4. Pasco P, Ison C, Munoz E, Magpusao E, Cheng A, Tan K, Lo R, Teleg R, Dantes M, Borres R, Maranon E, Demaisip C, Reyes M, Lee L. Understanding XDP through imaging, pathology and genetics. Int J Neurosci. 2011;121 Suppl 1:12-17. 5. Makino S, Kaji R, Ando S, Tomizawa M, Yasuno K, Goto S, Matsumoto S, Tabuena MD, Maranon E, Dantes M, Lee L, Ogasawara K, Tooyama I, Akatsu H, Nishimura M, Tamiya G. Reduced neurons-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. Am J Hum Genet. 2007;80:393-406. 6. Jamora R, Diesta C, Pasco P, Lee L. Oral pharmacological treatment of X-linked dystonia parkinsonism: successes and failures. Int J Neurosci. 2011;121 Suppl 1:18-21. 7. Aguilar J, Vesagas T, Jamora R, Teleg R, Ledesma L, Rosales R, Fernandez H, Lee L. The promise of deep brain stimulation in X-linked dystonia parkinsonism. Int J Neurosci. 2011;121 Suppl 1:57-63.

CASE STUDY
due to the observation that there was no male to male transmission. In addition, the high rate of dystonia in Panay Island led the first investigators to hypothesize a genetic founder effect, wherein a single mutation in a common ancestor is carried on in a geographical isolate due to the nonlethal nature of the disorder. The pattern of inheritance readily directed attention of investigators to the X-chromosome. The X-linked recessive pattern was firmly established with the analysis of more families in Panay. Family linkage analyses with polymorphic DNA markers that span the X-chromosome have narrowed the XDP critical region to Xq13.4 Sequencing this XDP critical region, Makino et al. reported a disease-specific retrotransposon in intron 32 of the TAF1 gene. Using expression analysis in brain tissues, they found that this mutation resulted in reduced expression of TAF1 and the dopamine receptor D2 gene in the caudate nucleus of XDP patients.5 Further studies into the genetic locus of XDP are underway, with the hope of eventually identifying the disease-causing gene, the protein product, and of carrying out animal models with which to study further the pathophysiology of the disease. Therapy is presently mainly symptomatic. Oral pharmacotherapy with anticholinergics, anti-Parkinsonian drugs, antihistamines, antipsychotics, and sedatives have produced variable results in small case series; these have not been systematically studied in randomized controlled trials to prove efficacy in relieving dystonia or parkinsonism in XDP with Class I evidence.6 A recent randomized placebocontrolled clinical trial conducted by the

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2012 Philippine Obstetrics and Gynecology Midyear Convention April 24-26 Theme : POGS Celebrates the Smiling Pinay Venue : LFisher Hotel, Bacolod City Info : Philippine Obstetrical and Gynecological Society Tel : +632 921 7557 Email : pogs@pldtdsl.net Website : www.pogsinc.org 24th Philippine Orthopaedic Association Midyear Convention April 26-28 Theme : Osteoarthritis Venue : Radisson Blu Hotel, Cebu City Info : Philippine Orthopaedic Association Tel : +632 667 3926 or 46 Email : secretariat@philorthopaedics.org Website : www.philortho.org 3rd Asian Facial Plastic Surgery Society (AFPSS) Congress April 29 to May 1 Philippine Society of OtolaryngologyHead and Neck Surgery Venue : Crowne Regency Hotel, Boracay Info : Asian Facial Plastic Surgery Society Tel : +632 633 8344 or 2783 Email : secretariat@pso-hns.org Website : www.afpsscongress.org

Conference Calendar

APRIL
49th Philippine Pediatric Society Annual Convention April 10-13 Theme : Pinoy Pedia Amidst Global Challenges Venue : Sofitel Philippines, Pasay City Info : Philippine Pediatric Society Tel : +632 926 6758 to 59 Email : ppsinc@webquest.com Website : tp://www.pps.org.ph 20th Pain Society of the Philippines Annual Convention February 5-6, 2010 Venue : Sofitel Philippine Plaza Tel# : +63-2 7230101 loc 5148 Fax# : +63-2 7268875 Website : www.philippinerheumatology. org Philippine College of Emergency Medicine Annual Convention April 17-18 Venue : Crowne Plaza, Mandaluyong City Info : Philippine college of Emergency Medicine Tel : +63 815 9911 Email : pceminc@gmail.com Website : www.pcemph.org 32nd Philippine Society of Nephrology (PSN) Annual Convention April 18-21 Theme : Nephrology in the 21st Century -Global Scope, team-based approach Venue : Crowne Plaza Hotel, Quezon City Info : Philippine Society of Nephrology Tel : +632 687 1198 or 1187 Email : info@psn.ph Website : mypsn.org

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MARKET WATCH

First Asian Acne Board Research Grant presented in Manila

The Asian Acne Board, a regional panel of the Global Alliance to Improve Outcomes in Acne, is pleased to announce that the 1st Asian Acne Board Research Grant in Acne was presented in Manila, Philippines at the Regional Congress of Dermatology on February 23, 2012. The winner of the Award, an unrestricted $10,000 USD grant, was Dr Hyuck Hoon Kwon from the Department of Dermatology at the Seoul National University College of Medicine in Seoul, South Korea. The title of Dr Kwons research is: Screening of natural products for the development of effective acne treatment agents and investigation of the molecular structure of active ingredients. Dr Kwons work was selected by the Award Committee of the Asian Acne Board which included Pr Yoshiki Miyachi from Kyoto University in Japan, Pr Dae Hun Suh from the Seoul National University College of Medicine in South Korea, Pr Chee Leok Goh from the Singapore Skin Centre in Singapore, and Dr Sewon Kang from Johns Hopkins University College of Medicine in Baltimore, Maryland in the USA. The Asian Acne Board Research Grant was developed to stimulate acne research in Asia. The Asian Acne Board Chair, Dr Kang commented: We are very pleased to have the opportunity to sponsor young researchers like Dr Kwon - his initiative and excitement for advancing knowledge in dermatology are commendable. Dr Flordeliz Casintahan, Chairman

Dr Hyuck Hoon Kwon

of the Acne Board of the Philippines agreed, adding that its highly important to stimulate research and interest in acne among Asian patients as the population of individuals of Asian descent continues to increase around the world. The Asian Acne Board includes 10 dermatologists with an interest in acne who come from Australia, India, Japan, Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand and the USA. The group was formed with a goal of focusing on the unique practices and clinical needs of Asian patients with acne; it is a regional sub-group of the larger worldwide Global Alliance to Improve Outcomes in Acne. In 2011, the Asian Acne Board published Consensus Recommendations about the treatment of acne in Asia in the Journal of Dermatology. The group meets semi-annually and continues to expand the knowledge base in the field of acne.

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MARKET WATCH

Centrum for adult nutrition

he demands of adult life can take a toll on any persons nutrition and eventually his/her health. To ensure the energy to keep up with a busy and stressful lifestyle, proper food intake, exercise and avoidance of vices may not be enough. Although a healthy diet and lifestyle is necessary to sustain energy, tight schedules and stress can limit the ability to meet specific daily recommended nutrient intakes. Certain vitamins and minerals have been studied to help maintain a healthy heart, cope with physical stress and promote/maintain healthy energy levels. Centrum is a complete multivitamin formula that can help meet an active adults daily requirements to help him/ her have the Energy to be Complete. Centrum contains 30 vitamins and

minerals, including essential nutrients needed by the body. Just one Centrum tablet a day gives six health benefits not just Energy, but also Immunity, Good Eyesight, Healthy Skin, Healthy Heart, and Strong Bones so you can be your best each day. Centrum is available in drugstores and supermarkets nationwide.

PGH Section of Dermatology releases comprehensive atlas

The Philippine General Hospitals Section of Dermatology recently published the book Atlas of Philippine Dermatology, a collection of cases systematically organized into a concise reference material. The atlas is for all physicians in general, including dermatologists and residents-in-training, and other health practitioners such as nurses, paramedical personnel, community and social health workers and students. The atlas provides steps on how to systematically examine the skin and recognize different lesions in order to arrive at a proper diagnosis. A section in the book features a compendium of interesting and rare cases. The book also includes a section on English-Filipino translations of common dermatological terms. Priced at P3,500, the atlas is available in PGH Section of Dermatology. For more information, call +632 526 2397 or 554 8400 local 5105-6 and look for Dr. Sharlene Chua or Dr. May Eusebio-Alpapara.

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MARKET WATCH

Galderma at the 20th RCD

Galderma, a Swiss Pharma company, served as Platinum Sponsor in the 20th Regional Conference of Dermatology held in Manila in February 2012. Distinguished experts from across the US, Asia and Europe shared new ideas and experiences during the sessions. Galderma, having the top rank in Dermatology Market globally (IMS December 2011) further exuded market leadership through the main brands highlighted during the conference Epiduo,

Cetaphil Restoraderm and the newly acquired Restylane. Galderma, indeed, is truly committed to the future of Dermatology.

Paradontax helps stop bleeding gums

Spitting blood when you brush? Bleeding gums can be one of the first signs of gum problems. And gum problems, if left untreated, is a major cause of tooth loss. It is important to consult your dentist once you experience bleeding gums. Parodontax is specially formulated for people who spit blood when they brush. When used every day, twice a day, it will help stop bleeding gums. Parodontax contains sodium bicarbonate, which with brushing, helps

remove the plaque bacteria that cause the initial inflammation and bleeding of gums. The special formula contains the natural ingredients peppermint, myrrh, chamomile, echinacea, mineral salt, rhatany and sage. It also contains fluoride to help prevent cavities so that you can use it every day with confidence. Brush with Parodontax twice daily and help stop bleeding gums. Parodontax is now available in leading supermarkets & drugstores nationwide.

SPONSORED SYMPOSIUM HIGHLIGHTS BULLETIN

LAST DECEMBER 5, 2011, AT THE MANILA HOTEL, EXPERTS IN THE FIELD OF OTORHINOLARYNGOLOGY CONVENED TO GET UPDATED ABOUT THE MANAGEMENT OF ALLERGIC RHINITIS.

Exploring new frontiers in allergic rhinitis: Effect of tonicity and preservatives on the efficacy and safety of nasal sprays
Jason Hwang Siew Yoong, MD
ENT Consultant, Gleneagles Medical Centre, Singapore

LS Mean Change from Baseline*

ntranasal corticosteroid (INCS) sprays are the most efficacious medication for allergic rhinitis. It achieves high drug concentrations in the nasal mucosa while maintaining minimal risk of systemic adverse effects. However, formulation characteristics have an effect on patient preference and tolerability. The preservatives commonly used are potassium sorbate and benzalkonium chloride (BKC). There are concerns with the use of BKC as it has ciliotoxic effects. Conflicting opinions about safety resulted from confounding factors like issues in the number of subjects, length of exposure, compliance, variation in concentration or anatomy and different endpoints. An investigation showed no effect on ciliary beat frequency (CBF) at 10% dilution and a reversible decrease in CBF at 50% dilution.1

Effectiveness of ciclesonide PAR Patients (Days 1 to 42)

0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 1 4 7 10 13 16 19 22 25 28 31 34 37 40
Time (Days)
LS Mean = least squares mean; CIC = ciclesonide *Data based on average total nasal symptom score for the intent-to-treat population Adapted from Meltzer EO, Kunjibettu S, Hall H, Wingertzahn MA, et al. Ann Allergy Asthma Immunol. 2007;98:175-181.

CIC 200 mcg OD Placebo

An INCS, ciclesonide, is a new corticosteroid indicated for use in seasonal or intermittent allergic rhinitis (SAR) for adults and children 6 years of age and older, and for perennial or persistent allergic rhinitis (PAR) for adults and children 12 years and older. It is well-tolerated and provides effective nasal symptom relief over 24 hours, with relief maintained during chronic use.2 Ciclesonide is formulated as a hypotonic suspensionthe first, and currently, the only INCS with this formulation. When a hypotonic suspension is administered intranasally, the difference in osmolarity between the suspension and the nasal mucosa drives water molecules to rapidly diffuse into the nasal mucosa. Increased viscosity and adherence of the suspending agents resulting from dehydration of the solution/suspension delay mucociliary clearance of the corticosteroid and increase the local drug concentration on the nasal mucosa. This is more effective compared to the medication delivery system of an isotonic suspension formulation; water droplets in an isotonic suspension slowly diffuse along with the drug into the nasal mucosa. A secondary consequence of the isotonic mode of action may be rapid clearance of the suspension into the esophagus, causing runoff down the back of the throat. Hypotonic suspensions, however, are retained in the mucosa, decreasing the amount of solution runoff down the back of the throat.

Ciclesonide nasal spray is a pro-drug. The inactive drug is hydrolyzed by intracellular airway esterases to the active lipophilic metabolite desisobutyryl ciclesonide (des-CIC). Once converted, des-CIC undergoes an additional metabolic step to form fatty acid conjugates (desCIC-oleate and des-CIC-palmitate). These fatty acid conjugates are largely inactive and have high binding affinity for the glucocorticoid receptor. Interestingly, in vitro data obtained from lung tissue demonstrated that these fatty acid conjugates of des-CIC can be converted back into des-CIC. Therefore, these fatty acid conjugates of des-CIC may represent a pool of metabolites available for reconversion into the active drug, allowing sustained anti-inflammatory activity.3 In a pivotal SAR trial with ciclesonide (Omnaris) nasal spray, a randomized, double-blind, parallel-group, placebo-controlled, multicenter study in adult and adolescent patients with SAR (median age 40 years, range 12 to 86 years) was done. After a baseline period of 7 to 10 days, 327 patients with ongoing SAR were randomized (163 to placebo and 164 to Omnaris nasal spray 200 mcg/day). Effectiveness of treatment was assessed based on patient-rated reflective Total Nasal Symptom Score (TNSS). These scores included 4 nasal symptoms (runny nose, itchy nose, sneezing and nasal congestion), each rated on a severity scale ranging from 0 (no signs or symptoms) to 3 (severe signs or symptoms).

At every time point, decreases from baseline were greater for the ciclesonide group than for the placebo group and these differences in favor of ciclesonide continued to increase over the entire treatment period.1 Also, a linear regression analysis of the response to treatment data was done. The results showed that patients with a higher baseline symptom score at randomization had a more robust change from baseline over the treatment period.1 Even in perennial allergic rhinitis, congestion, itching, sneezing and runny nose were improved after treatment.1 These are all possible with maintenance of efficacy and a demonstration of long-term safety.1,4 In 52 weeks of nasal spray use, no patient experienced a nasal septal perforation or nasal ulcer.4 Summary Ciclesonide is a new corticosteroid indicated for use in seasonal and perennial allergic rhinitis. The agent is approved for use in allergic rhinitis as a hypotonic suspension. Ciclesonide is a pro-drug that is activated upon interaction with endogenous intracellular esterases to desCIC. Ciclesonide and des-CIC have low oral bioavailability.4 Ciclesonide is well-tolerated and provides effective nasal symptom relief over 24 hours, with relief maintained during chronic use.2,3

References 1. Meltzer EO, et al. Ann Allergy Asthma Immunol. 2007;98:175-184. 2. Ratner PH, et al. Allergy Clin Immunol. 2006;118:1142-1148. 3. Data on file, Sepracor Inc. November 2007. 4. Chervinsky P, et al. Ann Allergy Asthma Immunol. 2007;99:69-76.
Editorial development by UBM Medica. The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage howsoever arising is hereby disclaimed. 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced by any process in any language without the written permission of the publisher. UBM Medica c/o MediMarketing Inc 11/F Equitable Bank Tower, 8751 Paseo de Roxas, 1226 Makati, Philippines T: +632 886 0333 F: +632 886 0350 E-mail: enquiry.ph@ubmmedica.com Web site: www.ubmmedica.com PH-ALT-051

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Conference Coverage

20th Regional Conference of Dermatology, 20-23 February, Manila, Philippines

Re-emerging skin infections present major challenge

Dr. Yves St. James Aquino

pstein-Barr virus (EBV), varicella zoster virus (VZV) and atypical mycobacterium are part of a growing list of re-emerging skin infections caused by organisms that have been relatively controlled in the past, but which have recently been reactivated due to changes in the environment, the organism or the host. We have been encroaching so much upon our environment because our population is growing, and we try to cut more trees, and we get exposed to weird insects that harbor weird organisms. And later we develop diseases, said Dr. Raul Destura, infectious disease specialist and director of the National Institute of Molecular Biology and Biotechnology under the National Institutes of Health-University of the Philippines, Manila, Philippines. Destura explained that these factors can contribute to either increased host susceptibility or increased disease transmission. The re-emergence of EBV, a human herpes virus that infects human mucosal epithelial cells and B lymphocytes, has been attributed to the increasing trend of immunosuppression in patients, such as those with cancer or autoimmune diseases, said Destura. Reducing immunosuppressive therapy is considered as part of treatment, as seen in reported series of cases involving patients with methotrexate-associated EBV. In this particular series, just removing methotrexate or discontinuing it actually resolved EBVassociated cutaneous lesions, explained

Destura. For atypical mycobacterium infections, which can present as abscesses, ulcerations or lymphangitis, emergence may be a result of immunosuppression and increase in leisure activities that involve skin-to-skin contact, according to Destura. Atypical mycobacteria are becoming more virulent especially for skin and soft tissue infections. The medications against atypical mycobacteria may include a combination of rifampicin, quinolones, doxycycline and/or erythromycin. There is still no standard duration of treatment, but most of the time its 6 to 8 weeks, said Destura. Known commonly to cause chickenpox in children and herpes zoster mainly in adults, VSV may manifest as painful vesicular eruptions with erythematous base in one to three dermatomal lines, facial weakness, post-herpetic neuralgia, among others. Besides immunosuppresion and an aging population, another potential contributor to the increase in incidence of VSV is the emergence of new manifestations associated with the disease. Destura added that recently, reactivated zoster presents with predominance of cutaneous pain without associated rash, in addition to neurologic manifestations, such as myelitis, meningoradiculitis, encephalomyelitis and ventriculitis. The clinical dermatologist remains an important player in the detection of these agents. And as the world gets smaller and smaller, the practice of medicine needs to become more connective and collaborative, concluded Destura.

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20th Regional Conference of Dermatology, 20-23 February, Manila, Philippines

Psoriasis studies show link with stress

Dr. Yves St. James Aquino tudies show that social aggressors and emotional stress can worsen symptoms of psoriasis, providing further evidence for the existence of a brain-skin axis, said Dr. Christopher Griffiths, foundation professor of dermatology in the University of Manchester, Manchester, UK. Griffiths and other members of the Dermatological Sciences Research Group within the School of Translational Medicine in Manchester are studying the two-directional relationship between psychological stress and skin disease. To understand the mechanism behind the psychosocial disability in psoriasis, one of the first studies performed by the group involved an automatic vigilance test. This psychological test was done by asking subjects to view a computer screen that showed words in different colors. The subjects were asked to identify the color and not to read the word. The researchers then measured the time it took for the subjects to identify the color after the word was shown. The more relevant the word is to that subject, the longer it takes for that subject to say the color. Condition-relevant words such as embarrassed, ridicule and itchy were used, as well as neutral ones like table and tree. Results show that subjects with psoriasis take much longer than normal volunteers when the words are relevant to their condition, while there is no significant difference in neutral words. What that means is that people with psoriasis are scanning their local

environment looking for cues about them having the disease. They misinterpret normal, everyday events as the fact theyve got psoriasis, explained Griffiths. Another study demonstrated how worry makes patients with psoriasis less likely to respond to psoralen + ultraviolet A (PUVA) therapy. Griffiths team assessed the severity of psoriasis, psychological distress, alcohol consumption, skin type in 112 patients be fore starting PUVA therapy. The group used the Penn State Worry Questionnaire to discriminate people who were low-worry (65 percent) and those who were high-worry (35 percent). The researchers found that high-level worriers took 1.8 times longer to respond to PUVA compared with the low-level worriers. And even if they did respond, it took them more treatments to respond. So high-worry or high-anxiety has a negative effect on response, said Griffiths. In order to promote a more holistic approach to psoriasis treatment, Griffiths and his colleagues investigated how cognitive behavioral therapy (CBT) may help alleviate symptoms. The CBT involved group therapy, teaching about psoriasis, stress reduction, and behavioral techniques to manage misinterpretation of other peoples reactions. Using the Psoriasis Area and Severity Index (PASI), they compared patients who received regular treatments and CBT with patients who were receiving regular treatments alone. After 6 weeks, those who had behavioral therapy had a significantly improved PASI; and after 6 months, the same group had even better improvement in dealing with emotional stress, said Griffiths.

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April 2012

Conference Coverage

20th Regional Conference of Dermatology, 20-23 February, Manila, Philippines

Smoking and its negative impact on lupus

Radha Chitale moking exacerbates cutaneous lupus and may prevent affected patients from responding to therapy, contributing to refractoriness. Smoking is a risk factor for getting lupus and having more severe disease, said Professor Victoria Werth, chief of Dermatology at the Philadelphia Veterans Administration Hospital in Philadelphia, Pennsylvania, US. Studies have shown that about 76 percent of refractory lupus patients those who do not respond to conservative therapy (including antimalarials) are smokers, compared to relatively lower percentages of refractory patients who are not, Werth said. Disease severity and disease activity is also higher in current smokers compared to never smokers or past smokers (P=0.017). [Arch Dermatol 2011 Nov 21. Epub ahead of print] In general, quality of life is impaired in patients with lupus. Treating refractory lupus helps patients have a higher quality of life, especially when it comes to emotional well being. Compared to patients with congestive heart disease and diabetes, those with mild cutaneous lupus had higher mean quality of life scores following treatment, in a study that included social and emotional indicators. [J Am Acad Dermatol 2011;64:849-58] Werth said these results indicated that patients with severe disease should get aggressive treatment. Typical approaches to treatment for

Smoking is a risk factor for developing lupus.

lupus include antimalarials (eg, chloroquine and hydroxychloroquine), immunosuppressive agents (thalidomide and its derivatives), and steroids (eg, dapsone, rituximab and retinoids). In a prospective cohort study, current smokers with cutaneous lupus responded to treatment with antimalarials alone significantly better than non-smokers (P=0.02), suggesting that physicians should try antimalarials in these patients, Werth said. [Arch Dermatol 2011 Nov 21. Epub ahead of print] However, the study also showed that smokers who do not respond to antimalarials, which are often the first-line treatments for reducing inflammation and controlling skin rash among patients with cutaneous lupus, usually do not respond to other therapies and end up in the refractory group. Its this group of patients that then become very challenged in terms of how best to manage them, Werth said. Although there is no hard evidence demonstrating that smoking cessation affects refractoriness, Werth said physicians should advocate for cutaneous lupus patients to stop smoking.

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20th Regional Conference of Dermatology, 20-23 February, Manila, Philippines

New sunscreen labeling in the US

Dr. Yves St. James Aquino

new sunscreen monograph announced by the US Food and Drug Administration (FDA) last year will take effect from June 2012. It requires that manufacturers of all sunscreen products sold in the US revise labeling of many existing products, and may involve retesting for sun protection factor (SPF) and broad spectrum performance. For the first time ever in the US, the UVA (ultraviolet A) testing and labeling requirements are now stated. For the longest time we only have SPF requirement. We dont have requirement as to how the UVA should be tested, said Dr. Henry Lim, director of the American Board of Dermatology. The UVA testing will be done in vitro, said Lim, using the critical wavelength method. Critical wavelength is defined as the wavelength below which 90 percent of the sunscreens UV absorbance will occur and is considered a measure of the breadth of sunscreen protection. The values may range from 290 to 400 nm. FDA requires a cut off of 370 nm in order for a product to be labeled as broad spectrum. There is no grade system or star system in anyway. It is just simply a pass or fail system, said Lim. Previous UVA test methods involved a star-rating system, which became the subject of debate because critics claimed the system was impractical and expensive. In terms of labeling, once the sunscreen product has passed the critical wavelength test, then it can be labeled as broad

Many existing sunscreens in the US may have to be retested for SPF and broad spectrum performance.

spectrum. The label has to have the same font as and should be adjacent to the SPF label, which is placed in front of the product. Products that earn greater than USD 25,000 are expected to apply the new label by June 18, 2012, while products that earn less must comply by June 17, 2013. In a statement released by the FDA, products that have SPF values between 2 and 14 can have the broad spectrum label if they pass the test, but only products that are labeled both as Broad Spectrum with SPF values of 15 or higher may state that they reduce the risk of skin cancer and early skin aging, when used as directed. The FDA also stated that products that are not broad spectrum will be required to have a warning that says the product has not been shown to help prevent skin cancer or early skin aging. According to Lim, the FDA will still allow old sunscreen products to be sold, but the new products to be put on shelf by the aforementioned dates must have the new label.

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Conference Coverage

20th Regional Conference of Dermatology, 20-23 February, Manila, Philippines

Syphilis detection more accurate with new tests

Elvira Manzano ovel dual point-of-care (POC) blood tests are more accurate than existing tests in the detection of active syphilis infection, says a leading dermatologist. Dual POC tests can detect both treponemal and non-treponemal antibodies required to establish a serological diagnosis, something not attainable with current POC tests. When both antibodies are pre-

are no longer infected. Chan explained that a positive treponemal test would require confirmatory nontreponemal assays RPR* or VDRL* to monitor serological response to therapy. The dual POC test is more sensitive and specific [than current POC tests]. Improved accuracy of POC syphilis tests gives us greater confidence to use them in situations that are not clinic-based, he said. It would enable clinicians to treat more

Improved accuracy of [the] POC syphilis tests gives us greater confidence to use them in situations that are not clinic-based patients and decrease time for spread of disease. This is important as syphilis cases are increasing in many parts of the word and in our region. The World Health Organization estimates that more than 12 million new cases of adult syphilis occur worldwide each year. In 2005, 4 million new cases were reported in Asia Pacific. As for treatment, penicillin is the drug of choice except in neurosyphilis. When there is allergy, doxycycline or erythromycin may be used, said Chan. He added that syphilis and HIV have the same modes of transmission. The presence of one is a risk factor for acquiring and transmitting the other. Therefore, we must do HIV testing of all patients with syphilis.
*RPR: Rapid Plasma Reagin *VDRL: Venereal Disease Research Laboratory

sent in the blood sample, three red-colored lines or spots would appear in the window of the device. Two spots/lines indicate old or treated infection. One spot/line indicates non-reactivity. Current POC tests detect only treponemal antibodies, said Professor Roy Chan, director of the National Skin Centre, Singapore and head of the Sexually Transmitted Infections (STI) Control Program Singapore. While inexpensive and can be done conveniently in the clinic, they are not as specific and can indicate old and new infections, Chan said. Like other treponemal tests, the main drawback is that they will be reactive with virtually every patient who has had syphilis and was treated. Continued use of the POC test as a sole diagnostic test inevitably results in overtreatment and repeated counseling in individuals who

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April 2012

Conference Coverage

20th Regional Conference of Dermatology, 20-23 February, Manila, Philippines

Personal Perspectives

I think its important for dermatologists to share their information ... Its important for us to be familiar with whats brewing, or whats becoming more and more innovative in Asia.
Dr. Anthony Paul Bewley Dermatologist, Barts and The London NHS Trust Whipps Cross University Hospital NHS Trust, London, UK

One of the interesting topics I think is STD [sexually transmitted diseases], because in my country there are so many cases. The information is something I can take home.
Dr. Dewi Martini Dermatologist, Fatmawati Hospital, Jakarta, Indonesia

We share similar dermatologic diseases, but because of our different locations and cultures, our approaches may be different. Its important that we get together once in a while and share what we know about skin diseases ... There are many ideas here in this convention and hopefully it does improve patient care.
Dr. Belen Dofitas Dermatologist, University of the Philippines-Philippine General Hospital, St. Lukes Medical Center Manila, Philippines

A lot of the topics are informative. Basically, the lectures were diseases that we commonly see in the out-patient department. Some are rare and worthy as case reports but are still very must-know.
Dr. Joahnna Villena Resident-in-training University of the Philippines-Philippine General Hospital, Manila, Philippines

April 2012 22nd Conference of the Asian Pacific Association for the Study of the Liver, 16-19 February, Taipei

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Conference Coverage

Protease inhibitors improve outlook in Hep C

Rajesh Kumar ovel direct acting antiviral agents (DAAs) currently under development promise to address a huge unmet need in the treatment of chronic hepatitis C. Protease inhibitors, the first generation of DAAs, offer much promise to hepatitis C genotype 1 (HCV-1) patients who respond poorly to the existing standard of care (SOC) comprising peginterferon/ ribavirin combination therapy, according to Professor Ed Gane, hepatologist and deputy director of the New Zealand Liver Transplant Unit in Auckland, New Zealand. Looking at the impact of HCV genotype on sustained virologic response (SVR), Gane said peginterferon and ribavirin for 48 weeks has been shown to be associated with a SVR rate of 82 percent in patients with HCV genotypes 2 and 3 compared with only 42 percent in those with HCV-1. [Lancet 2001;358:958-965]. About 25 protease inhibitors are currently in clinical development, with eight in phase III. Two such agents, telaprevir and boceprevir, were approved last year in Europe and the US for use in combination with the current SOC for the treatment of chronic HCV-1 in both treatment-nave and experienced patients. In the Phase III studies of boceprevir and telaprevir, their addition to peginterferon and ribavirin increased efficacy and shortened the duration of therapy in patients with HCV-1. As a result, the triple therapy is likely to become the new SOC, said Gane. However,

Protease inhibitors are novel direct acting antiviral agents that may help Hep C genotype 1 patients in particular.

it will not be suitable for patients with non-HCV-1 infection, or who are intolerant of or have contraindications to interferon, he said. Over half of the total global burden of hepatitis C is in the Asia Pacific region. Although latest data suggests the prevalence has stabilized and is actually falling, Gane said an ageing cohort and low rate of eradication due to poor treatment uptake means the proportion of those with advanced disease is steadily rising. The proportion of people who have cirrhosis is estimated to double over the

April 2012 22nd Conference of the Asian Pacific Association for the Study of the Liver, 16-19 February, Taipei

37

Conference Coverage

next 20 years. That will lead to an increase in related complications, he said. The Asia Pacific region has a marked variation of HCV genotypes: while HCV-1 dominates in north Asia, southern Asia has genotype 6 and accounts for a third of all the patients with this genotype while HCV-3 has become the predominant infection in the Indian sub-continent and in Australasia. Asians with HCV-1, however, respond better to the existing SOC than other races. The CHARIOT study involving 896 patients, including 116 Asians, showed dramatic difference in SVR rates in the two races. Treatment-nave Asians with HCV-1 had a better chance of responding to the 48-week treatment with a 360 g induction dose of peginterferon for the first 12 weeks, followed by a standard 180 g dose for 36 weeks in combination with ribavirin 1000-1200 g/day, said Gane. Four similar studies have confirmed better response among Asians with HCV-1,

apparently due to favorable patient IL28B CC genotype in Asian populations (70-90 percent) compared with Caucasians (3040 percent). But patients who failed to adhere to at least 80 percent of the prescribed therapy, irrespective of their genotype, had cure rates that were 80 to 90 percent lower than those who stuck with the regimen. The biggest issue in treatment of cirrhotic patients, however, is getting them to take the full dose therapy because their dose often needs to be reduced due to serious side effects, said Gane. The combination of multiple DAAs, which target different steps of HCV replication, should provide interferon-free treatment regimen. Both ongoing and planned studies will now determine which combination (protease, nonnucleoside polymerase, nucleoside polymerase, NS5A or cyclophyllin B inhibitors) and what duration of therapy will be required to optimize care, he added.

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April 2012 22nd Conference of the Asian Pacific Association for the Study of the Liver, 16-19 February, Taipei

38

Conference Coverage

Cirrhotic patients with infection need prompt care

Rajesh Kumar rompt and appropriate antibiotic treatment is essential in the management of cirrhotic patients with infection. While third-generation cephalosporins continue to be the gold standard antibiotic treatment for many of the infections acquired in the community, empirical antibiotic treatment of nosocomial infections needs to be adapted to local patterns of antibiotic resistance, said Dr. J. Fernandez, a liver specialist at the Hospital Clinic Barcelona, Spain.

also seen often. Over the past few decades, as the treatment regimen has become more complex, there has also been a gradual shift in the causative bacteria in hospital acquired infections from primarily gram-negative bacilli to gram-positive cocci, the latter having higher rates of infection, said Fernandez. Treatment failure rates of 18 to 41 percent have been reported for nosomical and other acquired infections in hospitals or other healthcare settings. Nosocomial infections are more resistant to third-generation cephalosporins, than community

Empirical antibiotic treatment of nosocomial infections needs to be adapted to local patterns of antibiotic resistance acquired infections, said Fernandez, while recommending revised treatment guidelines that would include another category of the treatment of pneumonia acquired in hospitals or other healthcare settings. Listing common problems and their solutions in the history of SBP and other infections in cirrhosis, Fernandez said low efficacy of treatment is addressed with third-generation cephalosporins, high rate of reoccurrence with antibiotic prophylaxis, high prevalence of of hepatorenal syndrome with albumin infusion, and high frequency of multiresistant bacteria with preventative measures and modification of antibiotic guidelines. However, restricting prophylactic antibiotics to high-risk populations will reduce the spread of multi-drug resistant bacteria in cirrhosis, he concluded.

Current treatment guidelines do not distinguish between community acquired and nosocomial infections, despite a huge difference between the two in terms of prognosis and bacterial resistance, said Fernandez, suggesting the status quo leads to higher proportion of failed treatments and higher mortality following nosocomial infections in cirrhotic patients. A quarter to one-third of cirrhosis patients end up catching an infection either in the community or during their stay at the hospital, and this remains the main cause of their mortality. Spontaneous bacterial peritonitis (SBP), urinary infection, pneumonia, secondary bacteremia and cellulitis are among the main infections found, although spontaneous bateremia, cholangitis and secondary peritonitis are

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April 2012

In Practice

Management of endometriosis: An approach for GPs

Dr. Beh Suan Tiong
Consultant Obstetrician & Gynecologist Behs Clinic for Women Thomson Medical Centre Singapore

A common progressive disorder Endometriosis abnormal growth of endometrium outside the uterus is a common, progressive disorder affecting women of reproductive age. The most common organs involved are the ovaries, the fallopian tubes and the pelvic region. Rarely, endometrial tissues or implants may be found in such remote areas as the lung, or the brain. The disease tends to progress under the repetitive stimulation of cyclical hormonal changes. Displaced endometrial tissues thicken, break down and bleed with each menstrual cycle as it would in the uterus. As the body cannot eliminate

not all of them develops endometriosis. The factors that might cause the tissues to grow in some women but not in others however need further studies. Alteration in the immune system and coelomic metaplasia transformation of one cell to the other may also contribute to the implantation of endometrial tissues, but all of these theories remain to be proven. Clinical features of endometriosis Endometriosis should be considered in women from after menarche to before menopause, who present with pelvic pain that worsens during menses. Pain severity is however not associated with surgical

Up to 30 percent of infertile women who seek treatment are diagnosed with endometriosis diagnosis or how the disease has spread (stage I = minimal; stage II= mild, stage III= moderate, stage IV= severe). Some women with moderate endometriosis may have intense pain while others with advanced endometriosis may have no pain at all. Another common symptom is dyspareunia painful sex, especially during deep penetration. Endometriosis can also cause fatigue, diarrhea, constipation, dysmenorrhea, menorrhagia or menometrorrhagia.

them, the tissues adhere to the surrounding organs causing intense inflammatory response, internal adhesions, and formation of ovarian cysts. Pathogenesis The exact cause of endometriosis is unknown but the most widely accepted theory involves retrograde menstruation the reflux of menstrual blood. Most women experience retrograde menstruation, but

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In Practice
include anatomical disruption of normal reproductive organs, ovarian dysfunction, toxic effects on the oocytes, sperms and embryos. As endometriosis is an estrogendependent condition, symptoms tend to improve or disappear during pregnancy and after menopause. Diagnosis A detailed history taking, especially on the relation of the symptoms to menses is important. The presence of a pelvic mass or a lump during palpation justifies an ultrasound to rule out ovarian cysts. The posterior fornix of the vagina should be assessed to check for thickening of the uterosacral ligaments. One biomarker that may be performed is CA-125, an elevated value of which may provide a supportive diagnosis. However, this test should not be performed during menses, when the level would be high, as it gives rise to false positive results. Definite diagnosis is confirmed by surgery, usually by laparoscopy. Clinical guidelines GPs may refer to UKs Royal College of Obstetricians and Gynecologists guideline on the management of chronic pelvic pain. However, practice standards may be slightly different for Asians and Caucasians. In the guideline, women with cyclical pain should be offered a therapeutic trial using the combined oral contraceptive pill or a gonadotrophin-releasing hormone (GNRH) agonist for a period of 3 to 6 months before having a diagnostic laparoscopy. The levonorgestrel-releasing intrauterine system could also be considered when appropriate.

A laparoscopic surgical photo of bilateral ovarian endometriotic cysts.

Ultrasound image of an endometriotic ovarian cyst.

Women may present with cyclical hematuria and dysuria if endometriosis has spread to the bladder. Rarely, chest pain and hemoptysis may occur if endometrial implants have proliferated to the lung; even headache and seizures if they have reached the brain. Infertility is another presenting complaint. Up to 30 percent of infertile women who seek treatment are diagnosed with endometriosis in the course of the diagnostic work-up for infertility. The mechanisms of how endometriosis interfere with fertility are not clearly understood, but

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In Practice
and voice changes. Oral contraceptive pills may also be used to prevent the endometrial implants from becoming active and to reduce the menstrual pain associated with endometriosis. These medical therapies are not advised in patients seeking conception because the drugs interfere with ovulation. Cystectomy and ablative surgery may ease symptoms and increase the chance of pregnancy if infertility is a problem.

When to refer A study by an international patient support group has shown that it takes an average of 9 years before a patient with endometriosis gets a definitive diagnosis. The true chronic aspect and full scope of endometriosis may not always be apparent. Thus, it is important to take a detailed history on the duration of pain, infertility and dyspareunia. If the patient is miserable, disturbed, and symptoms do not

One biomarker that may be performed is CA-125, an elevated value of which may provide a supportive diagnosis Definitive surgery, which includes hysterectomy and oophorectomy, may be an option for women with intractable pain and who no longer desire pregnancy. Conclusion There is no cure for endometriosis. The goal is to provide pain relief, restrict progression of the process and restore or preserve fertility in patients within the reproductive years.

improve despite medication, and CA 125 is positive, refer. Infertile women should be seen by an obstetrician-gynecologist early. It is also best to refer when in doubt. Management NSAIDs can be used in conjunction with other therapy, to relieve pain. Treatment in women who do not wish to become pregnant include hormonal therapy. Three hormonal stages should be achieved -- lower estrogen with GnRH agonist, increase progesterone level with one of the progestins , and increase androgen with danazol or gestrinone. GnRH agonist decreases follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in hypoestrogenism. Progestin counteracts estrogen and inhibits the growth of the endometrium. Many options are available, from the usual norethisterone to the more specific Visanne, and the choice depends on the tolerability of the patients to the various potential side effects. Danazol is a synthetic androgen that inhibits the growth of endometriosis but may cause hirsutism

Online Resources:
The Royal College of Obstetricians and Gynecologists www.rcog.org.uk/ Patient.co.uk www.patient.co.uk/health/ Endometriosis.htm The Endometriosis Association www.endometriosisassn.org/ The Endometriosis Network www.endometriosisnetwork.ca/

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April 2012

Calendar
Tel: (49) 6151 9518 89 2 Fax: (49) 6151 9518 89 3 E-mail: info@isdsworld.com Website: www.isdsworld.com 27th Asia Pacific Academy of Ophthalmology Congress 13/4/2012 to 16/4/2012 Location: Busan, South Korea Contact: Secretariat Email: regi@apaobusan2012.com Website: www.apaobusan2012.com/ 6th Biennial Congress of the International Society of Affective Disorders 18/4/2012 to 20/4/2012 Location: London, UK Contact: The Royal College of Physicians C/o Kenes UK Tel: (44) 20 7383 8030 Fax: (44) 20 7383 8040 Web: www.isadconference.com E-mail: isad@kenes.com World Congress of Cardiology Scientific Sessions 18/4/2012 to 21/4/2012 Location: Dubai, UAE Info: World Congress of Cardiology Email: congress@worldheart.org Website: www.world-heart-federation. org 24th European Congress of Ultrasound in Medicine and Biology 22/4/2012 to 24/4/2012 Location: Madrid, Spain Tel: (34) 913 61 2600 Fax: (34) 913 55 9208

April
10th Conference of European Academy of Occupational Health Psychology 11/4/2012 to 13/4/2012 Venue: Zurich, Switzerland Info: European Academy of Occupational Health Psychology Contact: Aditya Jain Email: conference@eaohp.org Website: eaohp.org/conference.aspx Drug Hypersensitivity Meeting 5 (DHM5 2012) 11/4/2012 to 14/4/2012 Location: Munich, Germany Info: European Academy of Allergy and clinical immunology Tel: (49) 89 54 82 34 62 Fax: (49) 89 54 82 34 43 E-mail: info@eaaci-dhm2012.com Website: eaaci-dhm2012.com/ HIV Immunologies and Preventive Technologies Conference 12/4/2012 to 13/4/2012 Location: London, United Kingdom Contact: Dr. Abubakar Yaro, Africa Health Research Organization Tel: (44) 79 3984-8586 Email: info@afrihero.org Website: www.eventsbot.com/events/ eb892234147 4th Spring Meeting of the International Society for Dermatologic Surgery (ISDS) 12/4/2012 to 15/4/2012 Location: The Leela Kempinski, Gurgaon, India

45

April 2012

Calendar
Tel: (82) 2 566 6031 Email: admin@woncaap2012.0rg Website: www.woncaap2012.org 2012 American Society of Clinical Oncology Annual Meeting 1/6/2012 to 5/6/2012 Location: Chicago, Illinois, US Tel: (571) 483 1300 Email: membermail@asco.org Website: chicago2012.asco.org 10th Royal College of Obstetricians and Gynecologists International Scientific Congress 5/6/2012 to 8/6/2012 Location: Kuching, Malaysia Tel: (603) 6201 1858 Email: info@rcog2012.com Website: www.rcog2012.com 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 Website: www.cardiologyonline.com E-Mail: Klimedco@ucla.edu 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) 22 906 9150 Email: esid@kenes.com Website: www.kenes.com/esid

Email: info@euroson2012.com Website: www.euroson2012.com III NWAC World Anesthesia Convention (NWAC 2012) 24/4/2012 to 28/4/2012 Location: Istanbul, Turkey Tel: (41) 22 908 0488 Fax: (41) 22 906 9140 Email: nwac@kenes.com Website: www.nwac.org

Upcoming
5th European Clinam Conference for Clinical Nanomedicine 7/5/2012 to 9/5/2012 Location: Basel, Switzerland Contact: Clinam, European Foundation for Clinical Nanomedicine Tel: (11) 41 61 695 9395 Fax: (11) 41 61 695 9390 Email: clinam@clinam.org Website: www.clinam.org American Thoracic Society International Conference 2012 (ATS 2012) 18/5/2012 to 23/5/2012 Location: San Francisco, California, US Tel: (1) 212 315 8652 Email: conference@thoracic.org Website: www.thoracic.org/go/ international-conference 19th WONCA Asia Pacific Regional Conference 24/5/2012 to 27/5/2012 Location: Jeju, Korea

47

April 2012

Humor

Well, exercising may not make you live longer, but you certainly will die healthier!

Did you wash your hands?

Ok Doc, Im awesomely impressed. Can you tell me now what should be done about my cholesterol?

You have a very serious illness Mrs. Lucas. So far thats all we know!

Good news honey. Dr. Carboni said that with proper medical care, you will live another ten minutes!

The tests are back. You are a Sagittarius!

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