Step-off approach to LABA asthma therapy under scrutiny

November 2012

Step-off approach to LABA asthma therapy under scrutiny

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IN PRACTICE Vaccination the key to global health

INDONESIA FOCUS Manfaat tanaman Phyllanthus niruri dan Vitis vinifera

Managing HFMD in primary care

CONFERENCE Metformin can be used more widely

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November 2012

Step-off approach to LABA asthma therapy under scrutiny Elvira Manzano

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he approach of discontinuing long-acting β2-agonist (LABA) therapy (‘stepoff’ therapy) in patients who achieve control of their symptoms on a combination of LABA and inhaled corticosteroids (ICS) may lead to exacerbation of symptoms and reduce quality of life, according to new research. A meta-analysis of five randomized controlled trials comparing step-off therapy with continued use of LABA and inhaled ICS medications found that the LABA step-off approach was linked to a rise in asthma-related impairment. Compared with patients who continued combination therapy, those who stopped treatment had fewer symptom-free days (608 vs. 622) and lower scores on questionnaires assessing quality of life and overall asthma control. They also required an average of 0.71 (95% CI 0.29 to 1.14) more puffs per day of a rescue bronchodilator and had a non-significant increase in use of oral corticosteroids (RR 1.68, 95% CI 0.84–3.38). There were no deaths and too few exacerbations in the studies to evaluate safety outcomes. [Arch Intern Med 2012; DOI:10.1001/archinternmed.2012.3250] The findings contradict the US Food and Drug Administration’s (FDA) ‘black box’ warning that LABAs, when given with ICS, should be discontinued as soon as asthma control is achieved. “In contrast to FDA recommendations, our analysis supports the continued use of LABAs to maintain asthma control,” said study author Dr. Jan L. Brozek from the department

of clinical epidemiology and biostatistics and medicine, McMaster University, Hamilton, Ontario, Canada. Manufacturers of LABAs are conducting further large-scale safety studies of their products, however the results of these will not be available for 5 years. “In the interim, the consistent trends that we identified for many asthma impairment factors, some of which were statistically significant, favor the continued use of LABAs,” said Brozek. Brozek and his fellow investigators cautioned that the studies were of short duration and had high withdrawal rates. Nevertheless, “our findings likely represent the current best evidence about stepping off LABA therapy in patients with asthma.” While there is consensus that LABAs have no role in asthma monotherapy, the findings help shift the burden of proof in the debate over stepped-down withdrawal of LABAs, wrote Dr. Chee M. Chan and Dr. Andrew F. Shorr, from the division of pulmonary and critical care medicine at Washington Hospital Center, Washington D.C., US, in an accompanying commentary. Moreover, they called on the FDA to reconsider the ‘black box’ warning for these agents based on the findings. “We hope that this meta-analysis helps to lift some of the black clouds in the debate surrounding LABAs,” they said. “Similarly, physicians must now reevaluate the contents of the black box for LABAs, particularly in individuals whose asthma is well-controlled with combination LABA and ICS therapy.”

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Do celebrities help public health campaigns? Alexandra Kirsten

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elebrities can help to promote public health and are effective in doing so, says a public health expert in Australia. While celebrities are not always health experts, unlike many health experts, they “often speak personally and bring compelling authenticity to public discourse,” wrote Dr. Simon Chapman, professor of public health at the University of Sydney, Australia, in a recent editorial published in the British Medical Journal. [BMJ 2012;345 DOI: http://dx.doi. org/10.1136/bmj.e6364] Critics of celebrities in health campaigns point to examples which have gone “badly wrong.” They focus on celebrity endorsement of “flaky complementary medicine and quack diets” or incidents where celebrities have veered away from the message. On the contrary, Chapman suggests there are many examples of celebrity engagement that have amplified news coverage about important neglected problems or celebrity involvement in campaigns to promote evidence-based health policy reform. Talking about the case of Australian cricketer Shane Warne, who accepted a six-figure sum to use nicotine replacement therapy to quit smoking, Chapman said “we should not expect perfect outcomes after celebrity engagement and need to be realistic about the need to sustaining public campaigns beyond their first burst.” When photographs appeared of the sportsman smoking again, many experts “failed to exploit” the important message about the risks of relapsing, said Chapman, “instead climbing on a cynical populist bandwagon about his alleged motives.” He also mentioned Australian singer Ky-

lie Minogue’s breast cancer, which “led to an increase in unscreened women in the target age range having mammography, but also to an increase in young women at very low risk seeking mammograms and thus being exposed to unnecessary radiation and falsepositive investigations.” The ambivalence about this effect reflects the debate about the wisdom of breast cancer screening, he said, “but it should not blind us to the potential value of celebrity engagement in important causes.” In response to Chapman’s comments, Dr. Geof Rayner, former chair of the UK Public Health Association and Honorary Research Fellow at City University London, England, said he remains concerned about the influences of celebrities who dabble in the public health arena. While celebrities might help to boost campaigns in the short term, Rayner said they “must tread a cautious path of support because of the risk that the celebrity becomes the story, not the campaign.” [BMJ 2012;345 DOI: http:// dx.doi.org/10.1136/bmj.e6362] Certainly celebrities help shift products, but according to Rayner this “has become mainstream marketing strategy” across society, even in politics. Rather than relying on media stunts, modern health campaigners “need to go on the offensive against junk food, alcohol, gambling, and other often celebrity linked, commercial propaganda.” Rayner postulated new measures to promote public health, for example campaign groups that “bring together the lobbying power of thousands of ordinary people through the internet.” “Some celebrities might help, but let’s not look for saviours, buoyed by the happy thought that the work is done when a celebrity is involved. That’s a lie too”, Rayner concluded.

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Vaccination the key to global health Excerpted from a lecture by Edith L. Maes (Ph.D.), senior research fellow, Maastricht School of Management, the Netherlands, at a media briefing in Kuala Lumpur, Malaysia.

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t has been shown by historical studies that there is a relationship between health and wealth, and that it really pays for governments to invest in health. Because of the dual relationship, there is a double dividend, especially in low- and middle-income countries. The reason is that healthy populations lead to economic growth. When people remain healthy, they also develop better physical and cognitive capabilities, so that in adulthood they become more energetic and active workers, which leads to higher incomes for their families, higher productivity and greater output, which is measured as gross domestic product (GDP) for the government. It is beneficial investing in health preventative measures that do not cost much or preventative measures which need an investment, but have a payoff in the short- and long-term. It is important at the individual level, family or household level, and the government level. Firstly, it is important at the individual level, especially to children, since they are vulnerable and contract diseases very easily because their immune system is not working well. If children are healthy, it’s better for the families because they will be able to develop their cognitive and physical abilities so parents will be able to continue working and generating an income. But if the child is sick often, the family incurs huge medical costs. In many countries, because of large out-ofpocket expenses, it also costs households a lot of savings, which indirectly has a long-term effect.

At government level, it is important because investing in health means actually investing in the workforce. So a healthy workforce is good for the country because it increases productivity and, as a consequence, its income. One measure to express health is life expectancy. Health can be defined in many ways, so epidemiologists and economists as well have taken one common measure, which is life expectancy, to express the benefits that accrue in a healthy population.

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Health can be defined in many ways...

Life expectancy is a measure at the population level – it’s an average among all individuals that survive in society. So, if large numbers of children die prematurely, the life expectancy will go down. In the early 1900s, most countries had low levels of income and life expectancy was 55 to 60 years. Gradually, especially in western countries, health improved because of better sanitation, potable water and preventive mea-

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sures like vaccines, and that increased the life expectancy in developed countries to 65 to 75. In 2010, when we cluster the countries, the high-income countries moved up to 70 to 82 years of age and their income also increased from US$14,000 to US$47,000, so their income increased accordingly to the increase in life expectancy. So that is how economies expressed the benefits of investing in health and tried to establish the relationship. Why is it that health in such nations and communities in general can improve? It is because the government decides to take measures, which can be very simple ie, educational programs to improve sanitation at home and building infrastructure to provide potable water for everyone. One of the measures that governments have been investing in is immunization for its short- and long-term benefits. In all the studies that have been done, the global community has recognized that vaccination is one of the world’s most important and cost-effective health interventions, with positive socioeconomic effects on society. [World Economics 2005;6:15-39] Key stakeholder benefits of vaccination include reduction in morbidity and mortality among individuals, which result in healthy families, a more productive workforce and herd immunity in society. It is in the interest of governments to invest in vaccination programs that are successful ie, that reach a coverage level of above 85 percent. When that level of protection is reached in the community, weaker and vulnerable people will also benefit from the decreased pool of pathogens. In the past 30 years, there has been a rapid increase in the number of vaccines. We are now at a point where we can prevent approximately 20 diseases through vaccination

programs, although sometimes it is only useful for certain target groups like travelers or healthcare workers.

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...vaccination is one of the

world’s most important and cost-effective health interventions

Looking at the evolution of vaccines – the very first vaccine, for smallpox, was actually experimentally tested in the 1800s. The person who tested the vaccine in farmers found that those who had been primed with pieces of the smallpox virus did not develop smallpox later in life. Gradually, the principle of priming the immune system started being recognized as being a very effective prevention method for certain diseases. The first few vaccines were developed for diphtheria, tetanus and polio – those vaccines were based on simple technology and can still protect against those killer diseases. The latest vaccines are based on complex technologies against rotavirus, pneumococcal diseases and human papillomavirus. These vaccines have taken a long time to develop, and are complex and more expensive than those developed in the 1950s and 1960s. The Global Alliance for Vaccines and Immunisation (GAVI) was founded in 2000 to fund vaccines in very poor countries that cannot afford any immunization programs or expand it with newer vaccines, and are also lacking a proper health infrastructure to provide vaccines to children in rural areas. The GAVI Alliance is a public-private partnership built on international solidarity and it devised a very innovative way of financing through donor fronts from a number of coun-

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tries and foundations including the Bill & Melinda Gates Foundation. There are a number of Western countries that have been pledging millions of dollars every year to vaccination, which can be used in the low-income countries with incomes below US$1,500 per person per year to give them an incentive to start developing their programs. Through the GAVI Alliance, rigorous government policies, and strengthening of vaccination programs at the country level, over 5.5 million lives have been saved since 2000. [GAVI Alliance Progress Report 2011. www. gavialliance.org/results/gavi-progress-reports/ Accessed on 24 September] The assessment of costs and effectiveness is becoming an increasingly important factor for policymakers faced with decisions about adding a new vaccine to national immunization programs.

To be able to compare with other studies and to compare between diseases, the WHO has come up with a metrics called DALY (disability-adjusted life years), which is a measurement of the gap between current health status and an ideal health situation where the entire population lives to an advanced age, free of disease and disability. This common measure allows governments to compare across diseases and technologies. We have seen many success stories in governments adopting the hepatitis B, pneumococcal and Haemophilus influenzae type B childhood vaccines. Investing in vaccination gives a high return in the short- and long-term for both individuals and society as a whole, and is based on the principle that health is a human right, so why would we deny it to ourselves or to our children?

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A4M-World Asia, 12-14 October 2012, Bali

Manfaat tanaman Phyllanthus niruri dan Vitis vinifera Hardini Arivianti

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alah satu topik pada ‘American Academy of Anti-aging Medicine Asia’, yang berlangsung tanggal 12-14 Oktober 2012 lalu adalah ‘Implementation of Herbal Medicine Based on Genes Expression for Maintaining Homeostasis in Aged People’ yang dibahas oleh Prof. Dr. dr. M Nurhalim S, MBiomol. Simposium kali ini dikolaborasikan dengan Kementerian Kesehatan dan Kementerian Pariwisata Ekonomi Kreatif. Sudah banyak studi di Indonesia yang meneliti berbagai herbal. Moeljoprawiro (2012) telah meneliti buah merah secara in vitro dan in vivo. Selain itu Astirin dkk (2008) juga meneliti efek ekstrak kasar (crude extract) Pandanus conoideus terhadap kanker payudara. “Riset menggunakan ekstrak kasar, karena ekstrak kasar tidak terlalu toksik dan persiapannya lebih sederhana. Namun masih banyak tantangan ke depan untuk mengetahui efektivitasnya secara ilmiah,“ jelasnya. Setelah mencapai lambung, ekstrak kasar selanjutnya akan dicerna oleh usus dan memasuki sirkulasi darah sehingga mencapai sel target. Tetapi tidak semua hasil digesti bisa memasuki sel karena lapisan membran di permukaan sel memiliki reseptor dan protein yang spesifik agar molekul-molekul tersebut dapat berinteraksi dengan reseptor yang ada. Pendekatan farmakoterapi dengan

melakukan ikatan molekul tertentu bisa dilakukan namun untuk daya antiaging dan antikanker memerlukan reaksi multipel karena untuk menjaga daya tahan hidup sel perlu banyak jalur dan tidak hanya bergantung pada satu molekul. “Hipotesa kami, aksi tunggal saja tidak cukup untuk memerangi sel-sel kanker dan proses penuaan, itu sebabnya kami sedang mengembangkan agen molekul yang dapat berinteraksi dan bereaksi secara multipel,“ tukas Prof. Nurhalim. Pakar biomolekuler dari Universitas Padjajaran ini telah menemukan beberapa gen yang dapat diintervensi oleh ekstrak kasar dari Phyllanthus niruri dan Vitis vinifera yaitu cell survival (p53, GAPDH), cell dormant/silence (p53, cyclin D1), cell arrest (p53, cyclin D1, PARP), cell resistant (cyclin D1, p53, bcl2), cell death (beclin1, casp3, RIP1), cell compe-

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tition (c-myc) dan cell senescence/non-dividing (p53, S-phase). “Dengan ini kita bisa menyesuaikan dosis optimal dari ekstrak kasar dan memonitor dengan senyawa aktif (obat kanker) yang ternyata hasilnya tidak banyak perbedaan. Senyawa aktif dapat membunuh sel kanker sekitar 95%, sedangkan ekstrak kasar mencapai 92%. Ini merupakan kesempatan besar untuk mengembangkan ekstrak kasar dari tanaman tradisional yang kita miliki.” Ekstrak kasar dari batang dan daun Phyllanthus niruri atau yang dikenal dengan nama meniran ini dibuat dengan cara ditimbang terlebih dahulu lalu dikeringkan dan diekstrak dengan etanol lalu dikeringkan hingga kadar air sangat minim. Rencana ke depan akan dikeringkan dibawah suhu yang tidak terlalu

panas dan dijadikan serbuk agar dapat dimasukkan ke dalam kemasan kapsul sehingga harga pun lebih terjangkau. “Uji yang sudah kami lakukan berupa kultur dan pada hewan. Kami sudah mendapatkan dosis, hanya tinggal mengarah ke uji klinis yang rencananya akan kami lakukan tahun depan.” Uji klinis yang akan dilakukan meneliti 2 hal, yaitu meniran (tunggal) dan meniran + biji anggur (gabungan). Secara tunggal, meniran dapat memicu perbaikan DNA dan bermanfaat dalam antiaging. Sedangkan meniran yang digabung dengan biji anggur, memiliki daya bunuh tinggi untuk memerangi sel kanker. “Ke depannya, kami akan memfokuskan pada penyakit-penyakit degeneratif, seperti obesitas, osteoporosis, diabetes, penyakit kardiovaskular, dll.

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A4M-World Asia, 12-14 October 2012, Bali

Studi klinis lanjutan isomaltulosa Hardini Arivianti

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ara pakar yang tergabung dalam tim peneliti isomaltulosa dari FKUI, yaitu Dr. dr. Tjhin Wiguna, SpKJ (K), Dr. dr. Saptawati Bardosono, MSc, dan Dr. dr. Rini Sekartini, SpA(K) bersama Dr. Eilardus Koen (Eiko) de Jong (‘Nutritional and Clinical Trial Monitor ’ dari FrieslandCampina), beberapa waktu lalu memaparkan hasil studi klinis lanjutan isomaltulosa. Studi pertama isomaltulosa telah dilakukan di Indonesia yang dilakukan pada 54 anak usia 5-6 tahun dengan jangka waktu konsumsi produk selama 14 hari. hasil studi ini menunjukkan hasil yang signifikan pada parameter tingkat perhatian (power of attention), tingkat perhatian berkelanjutan (continuity of attention) dan kecepatan ingatan (speed of memory) pada tiga jam setelah konsumsi. Tingkat kebutuhan energi otak berbeda dengan tubuh. Pada anak usia 1-6 tahun, rerata berat otaknya kurang dari 10% berat tubuh namun kebutuhan energinya lebih dari 40% energi tubuh. Fungsi kognitif yang optimal dan kemampuan melakukan tugas kognitif yang kompleks sehari-hari sangat penting dan sangat tergantung pada fungsi otak. Oleh karena itu asupan energi yang dapat bertahan lama sangat dibutuhkan guna mendukung perkembangan otak dan pertumbuhan fisik yang optimal. ”Dahulu kecerdasan dikaitkan hanya dengan IQ, kini kecerdasan tidak hanya

meliputi IQ namun juga mencakup EQ, dan faktor lain (nutrisi, lingkungan, dll) serta multiple intelligence,” jelas dr. Tjhin. Multiple intelligence ini meliputi motivasi, self-esteem, decision making, komitmen. Otak berinteraksi dengan lingkungan yang dapat berupa penyakit infeksi, nutrisi, imunitas, orang-orang dan keluarga, sensasi serta edukasi dan pelatihan. ”Guna mendukung perkembangan fungsi kognitif, anak tidak hanya memerlukan nutrisi tetapi juga perlu stimulasi,” tukas dr. Saptawati. Sebuah penelitian pada anak yang tidak diberi suplementasi zat gizi dan tidak distimulasi, menunjukkan perkembangan kognitif yang kurang berkembang. Penelitian lain tentang pentingnya zat gizi mikro – zat besi – membandingkan anak yang tidak anemia dan anemia yang diberikan suplementasi zat besi. Walau sudah diberikan suplementasi zat besi, fungsi kognitif pada anak yang anemia tetap tidak bisa mengejar anak-anak yang tidak anemia. Hal ini menjadi dasar perlunya pencegahan kekurangan zat besi pada anak. Selanjutnya Dr. Saptawati memaparkan, susu sangat superior karena sarat dengan zat gizi, protein, vitamin, mineral dan kalori, kecuali vitamin C. Walau kandungan kalori dan zat gizinya sama, susu yang diperkaya akan lebih baik dibandingkan dengan susu biasa. “Anak harus mendapatkan makanan lengkap, seperti salah satunya adalah susu, agar dapat

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mendapatkan manfaat dari zat-zat gizi yang terkandung di dalamnya sehingga perkembangan kognitif anak tetap terjaga hingga usia dewasa,” jelas dr. Saptawati. Studi lanjutan Setelah studi klinis pertama, FrieslandCampina kembali melakukan studi klinis lanjutan yang dilakukan secara acak pada 127 anak usia 5-6 tahun selama rentang waktu 3 bulan guna mengetahui konsistensi manfaat isomaltulosa terhadap kinerja kognitif anak. Subyek dibagi menjadi 4 kelompok yang diberikan 4 produk susu dengan susu pertumbuhan standar tanpa isomaltulosa sebagai referensi. Parameter studi ini meliputi baseline speed, memory search object, focused attention object, dan sustained attention. Latar belakang inisiatif studi lanjutan ini adalah ingin mengetahui lebih lanjut manfaat isomaltulosa pada jumlah partisipan yang lebih banyak dan rentang waktu yang lebih lama. Hasil temuan secara signifikan mengungkapkan isomaltulosa dalam susu pertumbuhan berpengaruh positif terhadap parameter ingatan dan perhatian dibandingkan dengan susu pertumbuhan standar. “Dari beberapa studi atau penelitian, disimpulkan isomaltulosa merupakan je-

nis karbohidrat yang menghasilkan glukosa yang memberikan energi lebih lama untuk otak. Ini sangat penting mengingat otak membutuhkan energi yang terus menerus sehingga suplementasi isomaltulosa menjadikan atensi dan memori pada anak lebih baik,” jelas Dr. Eiko. Mengenai studi lanjutan ini, Dr. Saptawati menambahkan, instrumen yang digunakan berasal dari Amsterdam dan ingin mempertegas hasil studi sebelumnya dan ternyata dengan instrumen yang berbeda, menunjukkan hasil yang sama atau konsisten. Selaku Spesialis Psikiatri Anak, dr. Tjhin memaparkan studi lanjutan ini sudah selesai dilakukan tahun 2011 lalu. Pengujian dilakukan terhadap kemampuan mengingat anak setelah melihat sederetan gambar dan mengulangnya. Hasilnya menunjukkan jumlah gambar yang lebih banyak dan waktu yang lebih cepat pada kelompok anak yang mendapatkan susu dengan tambahan isomaltulosa. Alat yang yang digunakan dalam studi lanjutan ini adalah AMT yang mengukur lama konsentrasi, memori secara visual dan mengetahui daya konsentrasi. Dengan alat ini diketahui kemampuan mempertahankan konsentrasi ternyata lebih panjang.

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Jangan abaikan kelenjar tiroid Hardini Arivianti

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arsinoma tiroid merupakan penyakit keganasan sistem endokrin yang paling sering ditemukan. Kira-kira 1020% pasien di endokrin menderita gangguan tiroid. Di Indonesia menempati urutan ke-9 dari 10 keganasan yang sering ditemukan, berasal dari kelenjar tiroid. Pada kelenjar tiroid cukup sering ditemukan nodul di dalamnya. Sekitar 4-8% nodul tiroid bisa ditemukan saat palpasi daerah leher dan sekitar 16-37% ditemukan saat pemeriksaan ultrasonografi. Biasanya nodul tiroid pada orang dewasa berupa nodul jinak dan hanya sekitar 5% yang ganas. Namun masalah keganasan pada kelenjar tiroid memiliki prognosis dan progresivitas yang lambat. Sesuai data RSCM selama 18 tahun, mencatat angka survival mencapai 75%. Hal ini diungkapkan oleh Prof.dr. Johan S Masjhur, SpPDKEMD, SpKN. Karsinoma tiroid dibagi menjadi 3 jenis yaitu berdiferensiasi baik (karsinoma tiroid papilifer/KTP, karsinoma tiroid folikuler/KTF, dan karsinoma sel Huthle), berdiferensiasi sedang dan tak terdiresensiasi (anaplastik). Insidensi KTP berkisar 80-85%, KTF mencapai 10-15% dan sel huthle 3-5%. Selaku Ketua Kelompok Studi Tiroid Perkeni, Prof. Johan lebih lanjut menguraikan, insidensi kanker tiroid tipe folikuler dan anaplastik lebih tinggi, terutama pada usia lanjut. Pada daerah yang kaya akan yodium (Irlandia), yang lebih menonjol adalah tipe papuler. Gambaran klinis berupa nodul tunggal (70-75%), sesak napas, perubahan suara, sulit menelan, dan pembesaran kelenjar getah

bening di leher. Insidensi kanker ini dipengaruhi oleh beberapa faktor yaitu demografi, lingkungan, usia, riwayat keluarga dan terpapar radiasi. Untuk mencegah keterlambatan terapi kanker ini memerlukan modalitas pemeriksaan karena tidak ada gambaran klinis yang khas. ”Sekitar 80-90% penderita kelainan kelenjar tiroid adalah perempuan. Namun, persentase keganasan pada laki-laki cukup tinggi sekitar 60-70% dari seluruh kasus kelainan tiroid pada laki-laki.” Laki-laki yang berusia diatas 50-60 tahun, angka keganasannya lebih tinggi karena stimulasi hormon TSH yang berbeda. Perlu diwaspadai terjadinya keganasan apabila teraba padat, keras dan bukan cairan (kistik), jumlahnya hanya satu dan tiba-tiba mengalami pertumbuhan yang cepat. Penatalaksanaan Guna mengurangi angka kekambuhan dan memperpanjang harapan hidup, perlu dilakukan pengelolaan terpadu. Pertama perlu dilakukan pemeriksaan laboratorium untuk mengetahui fungsi kelenjar tiroid dan petanda tumor yaitu memeriksa TSH, T3, T4, tiroglobulin dan kalsitonin serta foto polos bagian leher. Kedua, dengan biopsi jarum halus. Selain itu tindakan yang dilakukan bisa berupa operatif dan non-operatif. Operatif mencakup bedah terapetik bersifat ablasif berupa tiroidektomi total, tiroidektomi sub total, tiroidektomi mendekati total, lobektomi total, subtotal lobektomi dan ismolobektomi. Tindakan non-operatif berupa radioterapi, kemoterapi dan terapi hormonal dalam ben-

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tuk suplementasi. Pada kondisi pasien tidak lagi memiliki kelenjar tiroid (kondisi hipotiroid) perlu dilakukan substitusi hormon tiroid dengan dosis yang tepat. ”Pada pemeriksaan pemindaian tiroid atau skintigrafi, bila ditemukan nodul dingin soliter, 5-10% kemungkinan bersifat maligna dan bila ditemukan nodul panas, jarang bersifat ganas,” jelas Prof. Johan. Pada pemeriksaan USG tanda-tanda karsinoma meliputi hipekogenisitis, mikrokalsifikasi, tepian yang ireguler, peningkatan aliran noduler pada Doppler, dan invasi atau limfadenopati regional. Pasien yang sudah menjalani tiroidektomi total dan ablasi tiroid perlu di-follow up dengan mengukur kadar tiroglobulin (Tg) secara periodik dan whole scan body hingga remisi komplit tercapai. Pasien dengan hasil pemind-

aian yang negatif memiliki prognosis yang baik. Terdeteksinya kadar Tg dalam darah menandaan kanker masih ada, itu sebabnya perlu follow up kadarnya. Kadar Tg dan TSH setelah 1 tahun pemberian terapi primer merupakan faktor prediksi terhadap kanker ini. Pasien yang diterapi dengan tiroksin dosis supresif menunjukkan angka rekurensi yang jauh lebih rendah. Walau prognosis kanker ini sangat baik, namun sepertiga pasiennya mengalami rekurensi. Prognosis dikaitkan dengan usia, bila usia > 60 tahun maka tingkat rekurensi dan kematian lebih tinggi. Tipe papiler memiliki angka survival yang lebih tinggi dibandingkan tipe folikuler. Faktor prognostik yang sangat penting bagi penderita kanker tiroid adalah ukuran tumor dan kadar Tg 1 bulan pasca operasi.

The 14th International Meeting on Respiratory Care Indonesia 2012, 3-6 October 2012, Jakarta

Update seputar GOLD Guideline Hardini Arivianti

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ada ‘International Meeting on Respiratory Care Indonesia’ (RESPINA) ke-14 yang berlangsung tanggal 3-6 Oktober 2012 lalu, ‘Chronic Obstructive Pulmonary Disease’ (Penyakit Paru Obstruktif Kronik/PPOK) menjadi salah satu bahasan utama. “Penyakit paru ini akan semakin banyak kasusnya yang diakibatkan oleh rokok, peningkatan polusi udara dan meningkatnya usia harapan hidup. Faktor lain yang juga berpengaruh adalah nutrisi dan penyakit infeksi,” tukas Prof. dr. Faisal Yunus, SpP(K).

PPOK ini memiliki 3 fenotip yang mencakup sistemik (BMI rendah, pulmonary cachexia, dll), fisiologis (keterbatasan aliran udara, dispnea, hiperinflasi, dll) dan radiologik (emfisema, penyakit saluran udara). Gejala utama meliputi dispnea, batuk kronik dan sputum. Menurut GOLD guideline 2011, definisi PPOK adalah suatu penyakit yang sebenarnya dapat dicegah dan bisa diobati yang disebabkan oleh keterbatasan aliran darah yang bersifat progresif akibat inflamasi kronik. Perlu diperhatikan pada PPOK (menurut revisi

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GOLD) adalah faktor eksaserbasi dan komorbiditas yang memiliki peran dalam perjalanan PPOK secara keseluruhan dan dapat memperberat penyakit. “Salah satu faktor utama dalam pencegahan PPOK ini adalah dengan berhenti kebiasaan merokok pada pasien PPOK dan mengurangi risiko pajanan berbagai polusi asap rokok, gas berbahaya dll,” jelas Prof. Faisal lebih lanjut. Penegakan diagnosa klinis PPOK didasarkan pada adanya dispnea, batuk kronis dan produksi sputum serta ada tidaknya riwayat terpapar faktor-faktor risiko. “Pemeriksaan spirometri harus dilakukan dan bila hasil perbandingan FEV1 dan FVC < 0,70 berarti menandakan adanya keterbatasan aliran udara yang persisten atau PPOK.” Selanjutnya, Prof. Faisal memaparkan pentingnya penilaian pada PPOK. “Penilaian ini harus dilakukan guna menentukan tatalaksana, prognosis dan menentukan apa yang akan dilakukan dokter terhadap pasiennya.” Penilaian PPOK mencakup 4 hal yaitu gejala, derajat keterbatasan aliran udara, risiko eksaserbasi dan faktor komorbiditas. Kini gejala dapat dinilai dengan menggunakan ‘COPD Assesment Test’ (CAT) atau mMRC (modified Medical Research Council) Breathlessness scale. Pada skala mMRC, terdiri dari derajat 0 (sesak napas saat melakukan strenous exercise), 1 (sesak napas saat berjalan cepat di tempat datar atau saat berjalan menaiki bukit), 2 (pada tempat datar, saya berjalan lebih lambat dari orang-orang seusia karena saya merasa sesak, atau berhenti untuk mengambil napas saat berjalan kaki biasa), 3 (saya berhenti untuk menarik napas setelah berjalan kira-kira 10 meter atau setelah berjalan kaki beberapa menit pada tempat datar), dan 4 (tidak bisa pergi kemanamana karena sesak napas bahkan sesak pada saat berpakaian).

Berdasarkan nilai spirometri ada 4 derajat keparahan terbatasnya aliran udara nilai FEV1, se-bagai berikut ringan (FEV1 ≥ 80%), sedang (50% ≤ FEV1 < 80%), berat (30% ≤ FEV1 < 50%) dan sangat berat (< 30% FEV1). Eksaserbasi, komorbiditas dan terapi Menurut revisi atau tambahan pada guideline GOLD, penilaian terhadap eksaserbasi juga perlu dilakukan. Dibedakan, < 2x dalam setahun atau ≥ 2x setahun dan dilihat juga nilai FEV1 < 50% dari nilai prediksi. “Eksaserbasi menjadi penting karena merupakan kondisi akut PPOK yang ditandai perburukan gejalagejala (pertambahan batuk, produksi sputum, sesak) dan meningkat dibandingkan hari ke hari serta biasanya memerlukan obat lain (antibiotik atau kortikosteroid),” papar Prof. Faisal. Esksaserbasi dapat dipicu oleh beberapa faktor, yaitu infeksi virus pada saluran napas bagian atas (50%) dan dan faktor lain, misalnya polusi, kelelahan. Penyakit penyerta (komorbiditas) pun perlu dinilai. Yang tersering kardiovaskular, depresi dan osteoporosis. Menurut penelitian yang pernah dilakukan di RS Persahabatan, mendapatkan > 20% pasien PPOK mengalami depresi. Penatalaksanaan PPOK ada 2 hal utama yang harus dilakukan, yaitu mengurangi gejala dan mengurangi risiko. Mengurangi gejala dengan cara memperbaiki toleransi terhadap olahraga/aktivitas dan memperbaiki kualitas hidup, sedangkan risiko dapat diturunkan dengan mencegah penyakit menjadi progresif, mencegah/mengobati eksaserbasi dan menurunkan kematian akibat PPOK. Selanjutnya Prof. Faisal Yunus menjelaskan mengenai guideline GOLD 2009 yang menilai hanya dari spirometri, dan GOLD 2011 tidak lagi hanya dari spirometri namun juga

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Paisen

Karakteristik

Klasifikasi spirometri



A

Risiko rendah, gejala kurang

GOLD 1-2

≤ 1

0-1 <10



B

Risiko rendah, gejala banyak

GOLD 1-2

≤ 1

2+

≥10



C

Risiko tinggi, gejala kurang

GOLD 3-4

2+

0-1

<10



D

Risiko tinggi, gejala lebih banyak

GOLD 3-4

2+

2+

≥10

mencakup komponen-komponen lain yaitu eksaserbasi dan gejala. ”Makin banyak gejala, makin sering eksaserbasi maka PPOK makin memburuk, dan kemudian dapat berakhir dengan kematian.” Pengobatan yang diutamakan adalah berhenti merokok dan dilanjutkan dengan pemberian obat-obatan. Sesuai rekomendasi farmakoterapi GOLD 2011, pada PPOK yang stabil terapi utama dapat diberikan beta A2

Eksaserbasi/tahun

mMRC

CAT

agonis dan antikolinergik kerja lama. Bisa ditambahkan inhalasi kortikosteroid. Revisi guideline GOLD 2011 disimpulkan oleh Prof Faisal sebagai berikut spirometri diperlukan untuk penegakkan diagnosis PPOK ((FEV1/FVC < 0,70 yang memastikan adanya keterbatasan aliran udara), risiko eksaserbasi dan ada tidaknya komorbiditas. Kombinasi semua ini menentukan terapi yang akan diberikan.

Indonesia meraih penghargaan Dr. Guislain Hardini Arivianti

B

agus Utomo dari Indonesia terpilih sebagai pemenang pertama Penghargaan Dr. Guislain ‘Breaking the Chains of Stigma’ untuk upayanya yang tidak mengenal lelah memberikan pemahaman guna memerangi stigma skizofrenia, melalui organisasinya Komunitas Peduli Skizofrenia Indonesia (KPSI). Program Penghargaan Dr. Guislain ini merupakan penghargaan dunia berupa proyek kerja sama antara Museum Dr Guislain dan Janssen Research & Development, LLC. Dalam penghargaan tersebut, Bagus yang termotivasi oleh gangguan jiwa yang dialami kakaknya ini harus bersaing dengan 20 kan-

didat lebih yang berasal dari seluruh dunia. Karena kemenangannya, pria lulusan Universitas Indonesia ini mendapatkan hadiah sebesar US$ 50.000, yang akan digunakan untuk melanjutkan pekerjaan mengurangi stigma sosial penderita kesehatan jiwa dan gangguan otak. Komunitas Peduli Skizofrenia Indonesia (KPSI) yang Bagus dirikan kemudian menjadi wadah untuk berbagi pengalaman bagi para pasien dan keluarganya. Saat ini KSPI memiliki 6400 anggota dari berbagai daerah dan aktif melakukan edukasi kepada masyarakat. Perlu secara holistik “Penyebab gangguan jiwa adalah multi-

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faktorial, yang dapat berupa faktor genetik, organobiologik, sosiokultural, psikologi, dan lain sebagainya,” tukas dr.Tun Kurniasih Bastaman, SpKJ dalam acara berkaitan dengan penghargaan Dr.Guislain kepada Bagus Utomo beberapa waktu lalu. Sesuai Riskesdas (2007), mayoritas gangguan jiwa saat ini adalah gangguan jiwa ringan yang dijumpai pada 11,6% dari total populasi penduduk Indonesia yang berusia di atas 15 tahun. Data penderita gangguan jiwa berat di beberapa propinsi sebagai berikut: DKI Jakarta 2,03%, Aceh 1,85%, Sumatera Barat 1,67%, dan Jawa Barat 0,22%. Menurut kajian WHO, di tahun 2020 nanti depresi akan menempati posisi ke-2 setelah penyakit kardiovaskular. “Sementara skizofrenia di Indonesia sekitar 0,46%, yang memang prosentasenya kecil namun dampak terhadap pasien dan keluarganya sangat besar” lanjutnya. Penatalaksanaan tidak hanya memerlukan obat-obatan saja, lanjut dr. Tun, namun juga perlu hal lain misalnya psikoterapi, kegiatan pelatihan kerja dan sebagainya serta perlu dikerjakan secara holistik. Tingkat keberhasilan skizofrenia saat ini menurut ‘National Alliance for the Mentally III’ (NAMI) Amerika Serikat, adalah sekitar 60% bila dibandingkan dengan pasien den-

gan gangguan jantung (41-52%). Kemungkinan pemulihan maksimum tergantung konsistensi. Sekitar 75% pasien kambuh dalam waktu 1-1,5 tahun jika obat antipsikotik dihentikan atau tidak dikonsumsi teratur. Diperkirakan hanya sekitar 25% pasien dengan skizofrenia yang mengonsumsi obat secara teratur. “Kriteria sembuh bagi skizofrenia adalah bisa kembali berfungsi (pekerjaan, sosial, dll), dan diperkirakan sekitar 75-80% pasien dapat kembali berfungsi dan sekitar 25% akan terus mengalami kekambuhan. Kekambuhan ini biasanya terjadi akibat putus obat.” Terapi antipsikotik berupa oral dan injeksi kerja panjang (sekali dalam 2-4 minggu). Haloperidol merupakan generasi pertama yang diberikan secara oral dengan harga lebih terjangkau, namun dapat memberikan efek samping berupa tremor, air liur, berjalan seperti robot, dll. “Untuk menetralisir efek samping yang timbul secara individual ini dapat diberikan triheksipenidil (THP),” jelasnya. Mengenai lini pertama terapi skizofrenia, dr. Tun menjelaskan sedikit, sebenarnya kami sudah beralih ke generasi kedua yang efek sampingnya lebih ringan, dan sebagai lini pertamanya adalah risperidon.

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Tocilizumab, harapan baru artritis rematoid Hardini Arivianti

A

rtritis rematoid (AR) secara pasti belum diketahui penyebabnya hingga kini. Namun dampaknya dapat mempengaruhi kinerja sendi-sendi sehingga kualitas hidup pasien pun akan terganggu. Itu sebabnya diagnosa dan pengobatan yang tepat sangat diperlukan agar dapat membantu memperbaiki kualitas hidup pasien. Berbagai studi pengobatan AR ‘Indonesian Rheumatology Association’ (IRA) dan Roche Indonesia melakukan studi klinis tocilizumab PICTURE INA, yang melibatkan 39 pasien dengan AR selama periode Februari (2010)-Januari (2012). Studi ini dipimpin dr. Bambang Setyohadi, SpPD-KR yang dilakukan di lima pusat studi yaitu RSCM (Jakarta), RS Hasan Sadikin (Bandung), RS Dr Sardjito (Yogyakarta), RS Dr Soetomo (Surabaya), dan RS Saiful Anwar (Malang). Hasil studi menunjukkan, tingkat remisi pasien yang mendapatkan tocilizumab mencapai 85% dengan efek samping serius < 5%. Indikator remisi dinilai dengan menggunakan ’Disease Activity Score’ (DAS) dari 28 persendian atau DAS 28. Profil keamanan baik, dengan efek serius paska pengobatan di bawah 5%. Sebagai salah satu ‘Principal Investigator’ studi klinis di Indonesia, Prof. Dr. dr. Handono Kalim, SpPD-KR menjelaskan studi itu menunjukkan manfaat tocilizumab bagi pasien AR sehingga dapat memberikan

harapan baru dan memperbaiki kualitas hidup pasien nantinya. Menyusul studi PICTURE-INA, saat ini tengah berlangsung studi post marketing tocilizumab, yaitu studi ACT UP dengan senter penelitian yang diperluas hingga 9 senter termasuk Semarang, Medan, dan Denpasar. Studi ini mulai dilaksanakan awal Maret 2012, dan sebagai Principal Investigatornya adalah Prof. Dr. dr. Harry Isbagio, SpPDKR. Sepak terjang IL-6 Pengobatan AR diarahkan atas dasar mekanisme terjadinya penyakit ini yang salah satunya adalah mediator peradangan IL-6 (interleukin 6). Tocilizumab adalah penghambat antibodi monoklonal IL-6. Penelitian menunjukkan, terjadi peningkatan kadar IL-6 pada pasien AR. IL-6 merupakan mediator peradangan yang paling banyak ditemukan di sendi dan memiliki efek lokal maupun sistemik. Ada kaitan erat antara IL-6 dengan beratnya penyakit AR. Peningkatan kadar IL-6 berkaitan dengan gejala sistemik pasien AR, misalnya anemia, kelelahan, depresi dan penyakit jantung. IL-6 menyebabkan anemia karena dapat mengganggu proses penyerapan zat besi dari makanan dan pelepasan zat besi dari simpanan di makrofag. Anemia berkaitan dengan kelelahan, dan sekitar 30% pasien menderita anemia. IL-6 merupakan stimulator utama protein C reaktif (CRP) yang merupakan

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indikator inflamasi kuat. Kadar CRP tinggi berkaitan dengan penyakit kardiovaskular. Mengenal AR Penyakit ini merupakan penyakit autoimun progresif dan sistemik yang ditandai oleh peradangan kronis sendi tangan dan kekakuan, disertai gejala-gejala sistemik berupa kelelahan, anemia, dan depresi. Peradangan menyebabkan sendi terasa nyeri, kaku dan bengkak sehingga fungsi sendi hilang akibat kerusakan tulang dan tulang rawan yang berujung pada kecacatan progresif. Pasien dengan AR mengalami berbagai beban akibat penyakitnya mulai tingkat ringan hingga berat. Sebanyak 70% pasien merasakan nyeri sendi setiap hari, juga kaku sendi. Sayangnya, hingga saat ini belum ada obat yang dapat menyembuhkan penyakit ini. Menurut Dr. Ekowati Rahajeng, SKM, MKes selaku Direktur Penyakit Tidak Menular, DirJen Pengendalian Penyakit dan Penyehatan Lingkungan (P2PL), AR ini termasuk salah satu penyakit tidak menular yang terus meningkat. ”Malahan sekarang tidak hanya menyerang usia tua, pasien usia muda pun kini sudah ditemukan.” Prevalensi penyakit ini di Indonesia, Prof. Handono menuturkan, pada pasien >18 tahun sekitar 0,1-0,3% dan < 18 tahun mencapai 1/100.000 orang. Banyak pasien yang gagal diterapi dengan terapi yang ada sekarang dan sekitar 30-40% pasien tidak mendapatkan kontrol penyakit RA dari terapi yang ada sekarang serta > 50% tidak mencapai remisi penyakit (DAS28 ≤ 2,6). Pengobatan AR Tocilizumab yang baru mendapatkan ijin edar dari Badan POM ini, memiliki tar-

get sitokin IL-6. Ada kaitan erat antara IL-6 dengan beratnya penyakit RA. Tocilizu-mab yang merupakan antibodi monoklonal penghambat reseptor IL-6 bekerja dengan cara mengganggu jalur sinyal IL-6 dengan mengikat kedua reseptor IL-6 yang terlarut dalam darah dan yang terdapat di membran sel. Pengobatan ditujukan untuk tercapainya remisi dengan cara mengurangi nyeri, mengurangi inflamasi, menghentikan kerusakan sendi, memperbaiki fungsi sendi, dan membuat pasien nyaman. Pengobatan saat ini dilakukan dengan dua cara, yaitu untuk mengurangi rasa sakit dan pembengkakan pada sendi dengan menggunakan NSAID (Non Steroid Anti Inflammatory Drug) atau prednison dosis rendah. Sedangkan pengobatan lain adalah memperlambat atau mencegah proses penyakit dengan menggunakan ‘Disease Modifying Arthritis Rheumatoid Drug’ (DMARD) yaitu DMARD tradisional misalnya metotreksat, atau DMARD Biologis misalnya TNF Inhibitor, Rituximab, atau Tocilizumab. Penelitian juga menunjukkan, se-bagai monoterapi, tocilizumab lebih superior dibandingkan monoterapi dengan metotreksat. Efikasi tocilizumab juga lebih baik saat dibandingkan dengan obat biologi lain seperti rituksimab, penghambat TNF-alfa, dan etanercept. Dengan hasil positif terapi tocilizumab, tentu pilihan terapi pasien RA yang memberikan harapan semakin bertambah. Namun tocilizumab saat ini masih diberikan sebagai terapi lini kedua. Menurut dr. Handono lebih lanjut, guideline menyatakan bahwa sebelum diberikan obat biologi, pasien harus diterapi dengan DMARDs terlebih dahulu. Jika dalam waktu 2-3 bulan tidak ada perbaikan, baru digunakan obat biologi.

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Perlunya pemenuhan gizi anak Hardini Arivianti

T

ema simposium “The Importance of Early Life Nutrition: Blue Print of Legacy of Long Term Health” beberapa waktu lalu membahas pentingnya pemenuhan gizi anak di Indonesia, karena permasalahan beban ganda gizi (kekurangan dan kelebihan gizi) masih dihadapi Indonesia. Simposium ini diadakan oleh Perkumpulan Obsteri dan Ginekologi Indonesia (POGI) dan PT Nutricia Indonesia. Sesuai data Riset Kesehatan Dasar (RISKESDAS) 2010, jumlah anak dengan berat badan kurang (wasting) dan pendek (stunting) menurun dibandingkan data tahun 2007, namun terdapat tren kenaikan pada jumlah anak dengan kelebihan berat badan, dari 12,2% (2007) menjadi 14% (2010). Sebagai salah satu pakar obgin, Dr. dr. Noroyono Wibowo, SpOG(K) memaparkan fase pemenuhan gizi ibu dan bayi yang paling efektif yaitu harus dimulai sebelum masa kehamilan dan difokuskan pada 12 minggu pertama kehamilan karena inilah masa terpenting dalam pembentukan cetak biru genetik sebagai penentu kesehatan anak hingga dewasa nanti. Penilaian dini ibu hamil “Berat badan bayi dapat digunakan sebagai prediktor yang dapat diukur dari genetik, sebagian besar nutrisi dan lainnya (status kesehatan ibu, penyakit tertentu dll),” ungkap Dr. dr. Damar Prasmusinto, SpOG (K). Empat hal yang perlu dilakukan saat melakukan skrining genetik, yaitu genetik, abnormalitas kromosom, kelainan Mende-

lian dan kelainan poligenik. Pada periode perawatan antenatal, dokter perlu menanyakan riwayat kesehatan keluarga, minimal 3 generasi. Kromosom abnormal dapat terjadi pada ibu berusia > 35 tahun, seromarker abnormal, ada riwayat kromosom abnormal pada anak pertama dan orang tua, serta rekurensi abortus spontan. Kelainan Mendelian terjadi bila kedua orang tua merupakan carrier gen resesif otosom abnormal yang sama, usia orang tua > 50 tahun, dan tergantung jenisnya (otosomal, x-linked recessive/ dominant), contohnya kistik fibrosis, hemofilia A, hiperplasia adrenal kongenital, dll. Kelainan poligenik biasanya dipengaruhi oleh lingkungan atau ibu memiliki kelainan yang bisa diturunkan kepada anaknya, misalnya ibu memiliki defisiensi mineral tertentu, dsb. Untuk menentukan status nutrisi seorang ibu tidaklah mudah, misalnya berat badan sama namun memiliki tinggi badan yang berbeda. Ibu yang anemia juga sulit. Pada overt anemia, ibu tampak pucat, cepat lelah dll, sedangkan yang tidak tampak, dokter tidak akan tahu. Penilaian antropometri mudah dan murah, namun kerugiannya tidak bisa mendeteksi defisiensi protein, mikronutrien. Untuk lemak tubuh diukur dari cadangan lemak pada inter/intramuskular, sekitar organ dan saluran cerna, subkutan dan sumsum tulang, jaringan sarat pusat, dll. Olahragawan dan non-olahragawan, memiliki lemak tubuh yang berbeda walau berat badan sama. Pada ibu dengan kifosis, agak sulit mengukur tinggi badan, sehingga dilakukan den-

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gan teknik lain misalnya mengukur panjang tangan. Pengukuran antropometri juga mengukur lingkar lengan atas, ketebalan lipatan kulit, rasio lingkar pinggang dan panggul, serta lebar siku. “Sub-scapula skinfold thickness (SSFT) dapat memprediksi seseorang akan mengalami hipertensi atau tidak, jadi hal ini sangat bermanfaat,” lanjutnya. Body mass index (BMI) tidak dapat menjadi gambaran status nutrisi seseorang. Kadang BMI sama namun komposisi lemaknya sedikit, jadi sebaiknya tidak hanya melihat angka tetapi juga perhatikan kondisinya. Dikatakan dr. Damar, gabungan BMI dan skinfold thickness (SFT) dapat mengetahui apakah yang berlebihan itu lemak atau massa otot. Bila BMI tinggi + triceps skinfold thickness (TSFT) dan/atau SSFT rendah, berarti massa otot yang lebih banyak. Sedangkan bila BMI tinggi + TSFT dan/atau SSFT tinggi, menandakan komposisi lemak subkutannya tinggi. Selanjutnya, lingkar lengan atas dapat mengukur komposisi massa otot tubuh dan cadangan protein.

Pengukuran status mineral dan trace elements, misalnya zat besi, perlu dinilai tahapannya. Tahap pertama defisiensi zat besi dapat dinilai dari kadar serum atau feritin plasma, dan tahap ke-2 dapat dilihat dari kadar zat besi serum, iron binding capacity serum dan plasma total, protoporfirin eritrosit dan serum transferrin receptor. Sedangkan tahap ke-3 dapat diukur dari hemoglobin, hematokrit dan eritrosit. Selain itu, pemeriksaan yang tidak kalah penting adalah pemeriksaan klinis melalui anamnesa riwayat kesehatan ibu. Dijelaskan oleh dr. Damar, pemeriksaan laboratorium memiliki confounding effect. Bila hasil menunjukkan penurunan kadar retinol serum, berarti kemungkinan ada infeksi berat. Penurunan kadar vitamin E plasma juga bisa menandakan kemungkinan ibu mengalami infeksi seperti malaria, begitu pula bila terjadi penurunan pada kadar feritin (serum). Kadar zink plasma yang menurun menandakan kemungkinan ibu mengalami infeksi akut dan kronik.

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Local events calendar 21st Jakarta Diabetes Meeting Jakarta, 10-11 November 2012 Mercure Convention Centre Ancol, Jakarta Sekr : Divisi Endokrinologi dan Metabolisme, Fakultas Kedokteran Universitas Indonesia, RS Cipto Mangunkusumo, Jakarta Tel : 021-3907703, 3100075 Fax : 021-3928658, 3928659 Email : [email protected] Website : jakartadiabetesmeeting.com

Muktamar Ikatan Dokter Indonesia XXVIII Makassar, 20-24 November 2012 Hotel Grand Clarion & Convention, Makassar Sekr : Jl. Topaz 1/F-77, Panakkukang Mas, Makassar 90222 Tel : 0411-441565 Email : [email protected] Website : www.muktamaridi.com

7th Regional Scientific Meeting on Pediatric Dermatology Jakarta, 23-25 November 2012 Hotel Borobudur, Jakarta Sekr : Indonesian Pediatric Dermatology Study Group Ruko Grand Salemba, Jl. Salemba 1 no. 22, Jakarta Pusat 10430 Tel : 021-3161133 Email : [email protected] Website : www.rsmpd2012.com / www.perdoski.org

The Annual Scientific Meeting of Indonesian Society of Neurological Surgeons (PIT PERSPEBI) Medan, 27-29 November 2012 Hotel JW Marriott, Medan Sekr : Departement of Neurosurgery, Sumatera Utara University / Adam Malik Hospital, Jl. Bunga Lau No.17, Medan Sumatera Utara Tel : 061-8369114 Fax : 061-8369853 Email : pitperspebsi@pharma- pro.com

KOPAPDI XV Medan Medan, 12-15 Desember 2012 JW Marriot International, Aryaduta, Grand Aston, Medan Sekr : Departemen Penyakit Dalam Fakultas Kedokteran Universitas Sumatera Utara / Rumah Sakit Umum Pusat H. Adam Malik Lt. III, Jl. Bungalau 17, Medan

Tel/Fax : 061-4528075 Email : [email protected], [email protected] Website : www.kopapdimedanxv.com

The 6th National Symposium of Aesthetic Medicine and Cosmetic Surgery Jakarta, 15-16 December 2012 Hotel Grand Sahid Jaya, Jakarta Sekr : Jl. Semolowaru Elok I/11- 12A, Surabaya Tel : 031-34339288 Fax : 031-3957929 Email : [email protected]

The 1st ISICM National Clinical Case Conference On Intensive And Critical Care Medicine & Exhibition Makassar, 19-20 Januari 2013 Swiss-Belinn Panakkukang, Makassar Sekr : Indonesian Society of Intensive Care Medicine (PERDICI), Gedung Makmal Lt.2, Komplek FKUI, Jl. Salemba Raya No.6, Jakarta Pusat Tel : 021-685991557 Fax : 021-31909033 Email : [email protected] Website : www.perdici.org

PIPKRA : Towards Respiratory Healthy for the Future Jakarta, 7-10 Februari 2013 Hotel Borobudur, Jakarta Sekr : Poliklinik Paru Lt.2 RS Persahabatan, Jl. Persahabatan Raya No.1 Rawamangun, Jakarta Tel : 021-70726355,4893536 Fax : 021-4705684 Email : [email protected]

3rd Asian Society for Neuroanesthesia and Critical Care (ASNACC) Bali, 20-23 Februari 2013 Hotel Sanur Paradise Plaza, Bali Sekr : Departemen Anestesi, Fakultas Kedokteram Universitas Padjajdaran/ RS Dr. Hasan Sadikin Bandung, Jl. Pasteur No.38, Bandung Tel : 022-2038285, 2034853 ext 3221 Fax : 022-2038306

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In Practice

Managing HFMD in primary care Dr. K. Vijaya Director, Youth Health Division Singapore Health Promotion Board

H

and, foot and mouth disease (HFMD) is a common viral infectious disease that affects all age groups, but young children are especially susceptible. HFMD can be easily spread through direct contact with saliva, nasal discharge, feces or fluid from the blisters of an infected person. Generally, it is a mild self-limiting illness that resolves in 7-10 days. HFMD rarely recurs or persists, and serious complications are also rare. Although HFMD affects all age groups, children under the age of 5 are highly prone to infection because they interact closely with one another, in the classroom or on the playground, for example, at preschools. Human contact is one of the most common causes for infections to spread person to person. Individual cases of HFMD occur constantly but these can spiral into outbreaks affecting many children rapidly. For example, HFMD has become more prevalent in Singapore of late. Cases of HFMD infection have risen from 20,687 in 2011 to 31,590 as of September 2012. Education for prevention Primary care physicians are in the ideal position to educate parents and caregivers on the importance of hygiene and help prevent the spread of infection. Simple messages teaching parents and children the proper way to wash their hands is an effective method of preventing outbreaks.

The Singapore Health Promotion Board (HPB) advocates eight target areas for effective hand washing (Box). Diagnosing HFMD Primary care physicians need to pay close attention to symptoms to ensure that patients are diagnosed early so that infected children are prevented from spreading disease to others in the school. The burden of HFMD is likely to be concentrated within young, school-going children, but rates may vary. For example, the number of HFMD cases in Singapore reached a record high of 1,687 in May 2012, which far exceeded the epidemic level of 780 cases a week. The incubation period of HFMD lasts approximately 1 week and patients may only present with a sore mouth or throat. Therefore, symptoms may not be apparent initially and early symptoms may be mistaken for other illnesses. In addition to looking out for symptoms, physicians can also check if there are other cases of HFMD within the family or in the school the child attends. A child with HFMD usually presents with the following symptoms: • Fever for 2-3 days • Sore throat and runny nose • Rash (flat or raised red spots, some with blisters) on the hands (especially the palms), feet, and occasionally on the buttocks, arms and legs • Mouth ulcers • Vomiting and diarrhea • Tiredness and weakness A child is infectious throughout the duration of the illness.

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November 2012

In Practice

Laboratory testing is available to isolate and identify the causative agent. However, testing is usually not necessary because HFMD diagnosis is typically based on clinical grounds. Treating HFMD There is no specific treatment for the infection other than relief of symptoms. Treatment with antibiotics is not effective or indicated as HFMD is a viral infection. Easing the patient’s discomfort and helping them recover is the priority. Physicians should ask parents and caregivers to: • Encourage the child to drink plenty of fluids • Change to a soft diet (eg, porridge, pureed fruit) if the mouth ulcers are a problem • Medications can be provided to ease the discomfort, such as paracetamol syrup to relieve fever and pain • Keep the child at home to allow plenty of rest In most cases, HFMD is mild. However, a few children who are infected with the EV71 strain of the virus can become very ill, with signs and symptoms such as: • Disorientation, drowsiness and/or irritability • Fits • Severe headache, dizziness or neck stiffness • Breathlessness or turning blue • Dehydration – this can happen due to continuous vomiting, diarrhea or pure fluid intake as a result of painful mouth ulcers. The child will be very tired, have a dry tongue and may pass very little urine. A child with any of these symptoms should be immediately referred to a hospital emer-

gency department. In most cases, patients do not require follow up care. Physicians should closely monitor young children (especially infants) for development of dehydration. Rarely, patients with central nervous system manifestations of HFMD such as encephalitis or aseptic meningitis may require hospitalization. HFMD is highly contagious. A child is also susceptible to getting other infections when they have HFMD. Physicians can advise parents the following: • Keep the child away from public places. • Get everyone at home to wash their hands frequently with soap. • Keep child’s toys, books, eating utensils, towels and clothes separate from others, and disinfect them regularly • Inform the school, kindergarten or child care center as soon as possible. They can monitor other children closely and take additional precautions to prevent the spread of HFMD. • Keep the child at home until he or she is fully recovered, after the expiry of the medical certificate (MC) given by the family doctor. • Ensure that any siblings are well before sending them to the school, kindergarten, or child care center. Conclusion Primary care physicians need to educate parents and caregivers about keeping their child away from public places and schools during the infection period to avoid creating an outbreak. HFMD is present all year round in Southeast Asia, with seasonal outbreaks every year. Parents and caregivers should closely monitor their children to help prevent such outbreaks in childcare centers, kindergartens and schools.

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November 2012

Conference Coverage

48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany

EASD/ADA promote individualized therapeutic goals in T2DM Leonard Yap

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he European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have released a new joint position statement on the treatment of type 2 diabetes mellitus (T2DM). [Diabetes Care 2012;35:1364-1379; Diabetologia 2012;55:1577-1596] Designed to be less prescriptive than previous guidelines, the new statement advocates more patient involvement and gives guidance on the rational approach to the choice of therapy. This choice will now combine the best available evidence from the literature with the clinician’s expertise and the patient’s own inclinations. “Given the uncertainties in terms of type and sequence of therapies, this approach is particularly appropriate in T2DM,” said EASD president Professor Andrew Boulton from the University of Manchester School of Medicine and consultant physician at the Manchester Royal Infirmary in the UK. Ultimately, it is the patients who make the final decisions on their lifestyle choices and, to some degree the pharmacological interventions they use, said Boulton, adding that implementation of therapy occurs in the context of the patients’ real lives and relies on the consumption of resources. “The overarching goal should be to reduce blood glucose concentrations safely to a range that will substantially minimize long-term

The new statement focuses on the individual patient rather than ‘one fits all’ therapy.

complications, but always keeping in mind the potential adversities with treatment burden, particularly in the elderly who are more often exposed to multiple drug treatments,” Boulton said. The new recommendations of EASD and ADA called for individualized interventions in T2DM but also individualized goals for different patients. In the past, general recommendations regarding the intensiveness of glycemic therapy focused on a HbA1c target of below 7 percent. The statement emphasized the need to be pragmatic and to keep goals individualized.

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November 2012

Conference Coverage

The long-term effects of T2DM reveal themselves over the course of decades, which makes distinguishing the effects of medical interventions difficult, said Dr. Silvio Inzucchi, co-chair of the position statement and professor of medicine, Yale University School of Medicine, New Haven, Connecticut, US. Clinical investigators have been forced to use biochemical surrogates such as HbA1c to as-

Key points from the position statement: • Diet, exercise and education remain the foundation of any type 2 diabetes treatment program • Unless there are prevalent contraindications, metformin is the optimal firstline drug • A  fter metformin, combination therapy with an additional one or two oral or injectable agents is reasonable, aiming to minimize side effects where possible • Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain glucose control • Comprehensive cardiovascular risk reduction must be a major focus of therapy

sess the effectiveness of T2DM interventions. “How this might translate to actual effects on the quantity and quality of our patients’ lives remains largely unknown.”

‘‘

This approach is

particularly appropriate in T2DM

The precise glycemic target takes into account several factors including patient’s attitude and expected treatment efforts, risks associated with hypoglycemia and other adverse effects, disease duration, life expectancy, other co-morbidities, established vascular complications, and the patient’s own resources and support system. For example, some patients may feel that the weight gain associated with a particular diabetes therapy is unacceptable, and want other options to be considered. Older patients with multiple comorbidities will have different issues compared with a younger newly-diagnosed person that is otherwise healthy. The position statement pointed out that there is a need for numerous studies in specific subgroups of people of different ages and with different stages of diabetes, in order to assess the various possible combinations of glucose-lowering therapies.

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November 2012

Conference Coverage

48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany

Enterovirus may be linked to type 1 diabetes Leonard Yap

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n enterovirus infection may be a cause of type 1 diabetes (T1D) in some patients, says an expert. Evidence suggests that an infection of pancreatic islet beta-cells with one or more serotypes of enterovirus may contribute to the development of autoimmunity in some patients with T1D, said Professor Noel G. Morgan from the University of Exeter Medical School, UK. “The evidence has arisen from various sources, ranging from large-scale epidemiological studies undertaken across populations, to the isolation of productive virus strains from individual pancreas samples [in rare cases],” Morgan said. “However, despite the increasing weight of evidence, the hypothesis that an enteroviral infection might play a role in the etiology of T1D remains unproven.” Morgan’s research team studied a collection of pancreas samples recovered post-mortem from patients who died soon after a diagnosis of T1D. This cohort was used to study both viral protein expression and the establishment of anti-viral response mechanisms at the level of individual islet cells. The team’s aim was to determine whether individual islet endocrine cells displayed evidence of viral infection in human T1D and to establish, at the molecular level, how the cells responded to such infection.

The progression of human type 1 diabetes may be influenced by beta-cell enteroviral infection.

By monitoring expression of the enteroviral capsid protein, VP1, as a marker of infection, it was revealed that more than 60 percent of the pancreatic samples tested positive for enteroviral infection. However, within any given patient, only about 20 percent of insulin-containing islets expressed immunoreactive VP1 and the overall proportion of available β-cells that expressed VP1 was small (about 5 percent). A similar prevalence of immunopositivity was confirmed in a smaller, but more contemporary, cohort from within the Juvenile Diabetes Research Foundation (JDRF) nPOD series from the US. Morgan and co-workers also monitored the expression of various other proteins, including protein kinase R (PKR) and myeloid cell leukemia-1 (Mcl-1), in concert with VP1.

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November 2012

Conference Coverage

PKR is an enzyme responsible for the activation of antiviral cascades within cells and is known to be induced during enteroviral infection. It is activated by the presence of viral dsRNA and leads to the rapid arrest of global protein synthesis by virtue of increased phosphorylation of the initiation factor eIF2α. Mcl1 is an anti-apoptotic protein which is subject to rapid turnover in cells, such that it is degraded quickly during the translational arrest that ensues following the activation of PKR. “Collectively, our data imply that enteroviral infection can be detected within a small proportion of β-cells in the majority of patients with recent-onset type 1 diabetes,” said Morgan. “Moreover, this infection is associ-

ated with the mounting of an active antiviral response. The data are consistent with the hypothesis that the progression of human type 1 diabetes may be influenced by beta-cell enteroviral infection.” Morgan believes that it is entirely possible that additional mechanisms beyond enteroviral infection can act as triggers leading to islet autoimmunity. “It is also probable, however, that enteroviruses may be able to maintain a low-level persistent infection of islet cells under conditions when they produce minimal amounts of viral protein,” he added. “Hence, the failure to detect them by analysis of protein production in tissue sections does not necessarily mean they are not there.”

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28

November 2012

Conference Coverage

48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany

Stroke risk high in diabetes patients Alexandra Kirsten

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ype 2 diabetes is associated with an increased risk of stroke in the long term, suggests new research. A recent large-scale study involving 1,334 patients with type 2 diabetes found a cumulative stroke incidence of 12 percent over a 10year follow-up period. “The morbidity and mortality due to stroke in persons with type 2 diabetes mellitus is 3 to 4 times higher than in the general population,” explained study author Dr. M. Bernas from the department of internal diseases and diabetology at Warsaw Medical University, Warsaw, Poland. The study patients, who were all attending the same outpatient diabetic clinic, included 597 men and 737 women, and had an average age of 62.6 years and a mean duration since diabetes diagnosis of 9.4 years. Clinical determinants such as BMI, blood pressure, fasting and postprandial glycemia, cholesterol, triglycerides, creatinine, albuminuria, and co-existing complications and co-morbid states, were recorded at baseline and every year during the 10-year study period. Morbidity and mortality due to stroke were determined and correlated with potential risk factors every year separately and as a cumulative value for the whole period. At baseline, 62 patients (4.6 percent) had a previous history of stroke. In the 10-year period, 135 new episodes of stroke (in 7.5 percent

Type 2 diabetes has been shown to be a long-term risk factor for stroke.

of patients) were observed. The cumulative incidence of stroke was 12.1 percent, which equated to 10.8 cases per 1,000 patient-years. The cumulative mortality due to stroke was 11.0 percent. Statistically significant risk factors included age (95% Cl 1.03-1.07; P<0.001), fasting glycemia (95% Cl 1.17-3.39; P<0.05), daily albuminuria (95% Cl 1.02-4.06; P<0.05), atrial fibrillation (95% Cl 1.39-6.09; P<0.01) and smoking (95% Cl 1.17-3.00; P<0.01). These are “the main objectively established clinical risk factors for stroke,” summarized Bernas. This information should be taken under consideration in building up an individual plan of stroke prevention since “the efficacy of the prevention of stroke stands up as the ‘hot’ problem in diabetes mellitus care”, she concluded.

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November 2012

Conference Coverage

48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany

Insulin infusions beneficial in diabetics post-stroke Alexandra Kirsten

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atients with type 2 diabetes who experience an acute episode of stroke seem to benefit more from continuous intravenous insulin infusions than from intermittent subcutaneous injections. “Hyperglycemia is associated with [a] worse outcome in stroke patients,” said Leonid G. Professor Strongin from the State Medical Academy, Nizhny Novgorod, Russia. “The benefits of intravenous infusions for blood glucose control in patients with stroke and type 2 diabetes mellitus are proved at a target glucose level less than 7 mmol/L, but it is not so obvious for the more acceptable range of 7.8-10 mmol/L”, he explained. Strongin and colleagues conducted a clinical study to compare the efficacy and safety of the two different insulin delivery methods in patients with type 2 diabetes who had experienced a stroke. A total of 73 patients were subdivided into two comparable groups within 24 hours of the stroke event, with one group assigned to receive continuous insulin infusions and the other intermittent subcutaneous insulin injections, in order to achieve blood glucose levels between 7.8 and 10 mmol/L. Overall, 97 percent of the patients in the insulin infusion group achieved the glucose target compared with only 71 percent

of those in the injection group (P=0.012). The mean daily glycemia level was 8.7 mmol/L in the infusion group and 9.7 mmol/L in the comparison group (P=0.025). Additionally, the infusion group reached the target glucose levels faster (2-3h vs. 3-6h, P=0.0019) and showed a smaller amplitude of fluctuations of glycemia (0.95 mmol/L vs. 5.3 mmol/L, P<0.01). The frequency of hypoglycemia was significantly lower in the infusion group than in the comparison group (9 percent vs. 22 percent, P=0.037). Patients in the basal group presented with better scores in the Barthel Activities of Daily Living Index (BADLI) at the time of discharge (45 vs. 20 points P<0.01) and after 6 months (62 vs. 47, P=0.006). However, there were no significant differences in hospital mortality between the groups: in the infusion group 25 percent of the patients died, in the control group 32.4 percent died (P=0.32). “Glucose control using continuous intravenous insulin infusions has advantages in regressing neurological deficit, improving functional recovery and decreasing risk of hypoglycemia”, concluded Strongin. But, “the impact of routes of insulin administration on 6-month survival could not be proved.”

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November 2012

Conference Coverage

48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany

Exercise lowers CV risk in diabetics Alexandra Kirsten

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new study has reported that leisure-time physical activity (LTPA) can significantly reduce the risk of cardiovascular (CV) events in patients with type 2 diabetes. Dr. Björn Zethelius and colleagues from Uppsala University in Uppsala, Sweden reviewed data on leisure-time physical activity from 15,462 patients with type 2 diabetes registered in the Swedish National Diabetes Register (NDR). In their study, patients were grouped as either “low physical activity” (no regular exercise or exercise once per week) or “regular exercise” (between three times per week and daily exercise). If a patient died during the course of the study, his or her last recorded physical-activity level was used for the analysis. The yearly recorded data showed that regular exercisers were significantly less likely to have a cardiovascular event or to die either from cardiovascular disease or any other cause. The level of LTPA was related to fatal CV outcomes and all-cause mortality independently of conventional CV risk factors in type 2 diabetes. An increased LTPA level during the follow-up seemed to lower both CV risk and mortality in diabetic patients. Those in the study who reported doing little or no physical activity at baseline but who managed to increase their regular exercise to at least three times per week by the end of the study period (average 4.8 years) had even greater benefits. Compared with individuals who did not improve their exercise hab-

its, the number of CV-related deaths among diabetics who increased their exercise levels fell by 67 percent (95% CI 0.17-0.60). Rates of all-cause mortality were reduced by almost the same degree (95% CI 0.25-0.49). “In general, It’s never too late to increase your physical diabetics are activity, a recent study suggests considered to be less likely to engage in a regular exercise program than the general population,” stated the researchers. However, approximately 1,800 patients moved from a low physical-activity category into a higher physical-activity level over the course of the study. “We consider physical activity and dietary advice as the basal treatment for diabetes, and when it fails, different types of pharmacological treatment are added,” Zethelius explained. “But what this study shows is that it’s never too late to increase your physical activity. Even when you are on medication, if you increase your physical activity, you will lower your risk for cardiovascular diseases.”

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November 2012

Conference Coverage

48th Annual Meeting of the European Association for the Study of Diabetes, 1-5 October, Berlin, Germany

Metformin can be used more widely, study suggests Alexandra Kirsten

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he effectiveness and overall benefits of the antidiabetic drug metformin far outweighs its risks, even in patients with renal impairment, according to a Swedish study. “The long-term effectiveness and safety of glucose-lowering medications are under debate,” said lead study author Dr. Nils Ekström from the Sahlgrenska University Hospital in Sweden. Metformin in particular is normally not prescribed for patients with reduced kidney function because the risk of adverse effects is widely regarded as unacceptably high. Ekström and his colleagues evaluated the risks of cardiovascular disease, lactic acidosis, serious infections and mortality in 51,675 patients with type 2 diabetes registered in the Swedish National Diabetes Register (NDR). The patients were grouped according to their medication (ie, metformin monotherapy, insulin monotherapy and therapy with other oral hypoglycemic agents). The researchers analysed risks of fatal/non-fatal cardiovascular disease (CVD), acidosis/serious infection and all-cause mortality in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. The mean follow-up of the study was 3.9 years – equivalent to more than 200,000 patient-years at risk. After adjusting for clinical characteristics, risk factors and treatments, insulin monother-

apy was associated with an increased risk of fatal and non-fatal CVD and all-cause mortality compared with metformin monotherapy (95 % CI 1.07-1.29 and 95% CI 1.19-1.50, respectively). In subgroup analyses, metformin was not associated with an increased risk of any of the outcomes in patients with eGFR 3045, 45-60, or >60 mL/min/1.73 m2 compared with all other hypoglycemic agents. Of note, on a subgroup of patients with renal impairment (eGFR 45-60 mL/min/1.73 m2), metformin showed a reduced risk of any acidosis/serious infection and all-cause mortality. “In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects. These results support the less strict approach to metformin use in patients with renal impairment advocated in most guidelines”, the researchers said. ”Thus, the drug can be prescribed for many more patients with diabetes than is currently the case.” According to Ekström, a number of other countries already recommend metformin for patients with mild kidney impairment. Nevertheless, “it is important to keep in mind that the results are for patients with mild to moderate kidney impairment,” he pointed out. “Metformin still cannot be recommended for patients with severe kidney impairment and should be prescribed with great caution for those patients.”

32

November 2012

News

Keep older drivers on the road, says expert Alexandra Kirsten

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andatory medical screening of older drivers – which has been imposed in some European countries and is proposed in the UK – is not evidencebased and may have dangerous consequences, a gerontologist has said. “Age-related medical screening should be abolished,” said Professor Desmond O’Neill, consultant physician in geriatric and stroke medicine at Trinity College, Dublin, Ireland, recently in the British Medical Journal. [BMJ 2012;345 DOI: 10.1136/bmj.e6371] Older drivers not only have an enviable crash record, but they also raise traffic safety among other generations, explained O’Neill. “The risk of serious injury to children is halved if driven by grandparents rather than parents,” he said, “yet the belief that older drivers pose a disproportionate risk to other road users refuses to die.” His suggestion that medical screening for older drivers be abolished does not imply professional neglect of their medical fitness to drive, he added. O’Neill said a recent report from a UK parliamentary charity that “overstates the risk of older drivers and recommends training for them” was disappointing and an unnecessary measure of “dubious value.” According to him, several practitioners are confusing increased risk of death because of fragility with crash risk. In addition, they may lack sufficient gerontological training to understand that the positive aspects of ag-

It is a misnomer that older drivers pose high risk to other road users.

ing, such as wisdom and strategic thinking, help in adaptation and compensation to the “vicissitudes of later life.” Previous studies on medical screening showed a hazardous shift from protected to unprotected road user, explained O’Neill. When the Danish government added a cognitive screening test to the medical screening test for older drivers, it did not reduce the rate of older people dying in car crashes but significantly increased the risk these people had of being injured as pedestrians. We need flexible transportation options responsive to the needs of older people and car safety features designed with the elderly in mind, he said. The emergence of better guidelines for doctors dealing with opportunistic screening among older patients in the clinical setting is of enormous value. Rather than mass screening, “we should focus on evidence based innovations, such as restricted licensing and rehabilitation, for people with agerelated illness.”

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November 2012

Hepatitis

Children or young adults with CHB may benefit from earlier treatment Radha Chitale

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reating chronic hepatitis B (CHB) in younger patients before they begin to show signs of liver damage could help to control or clear the disease better than starting treatment later, researchers said. “When patients are young, from children up to young adults, the disease is not very aggressive,” said lead researcher Professor Antonio Bertoletti, director of the Infection and Immunity Programme at Singapore’s Institute for Clinical Sciences at the Agency for Science, Technology and Research (A*STAR). “The assumption that has always been present is that… these patients don’t have any strong immune response against the hepatitis B virus.” In the first study to compare young patients and adult patients, who were infected at birth or in the first year of life and had similar disease profiles, the researchers isolated T-cells from CHB patients of various ages and measured levels of inflammatory cytokines and the number of HBV-specific Tcells. [Gastroenterology 2012;143:637–645] Their analysis showed that inflammation levels in younger patients were similar to those of healthy control subjects and that their immune systems were primed with higher levels of T-cells that fight off HBV infection than adults with CHB. International guidelines recommend delaying treatment for CHB until the liver begins to deteriorate as a result of the increased immune response to the virus. But the results did not support the theory that younger patients with CHB existed in a state of asymptomatic “immune tolerance”,

Study results do not support the international guidelines recommending delayed treatment for CHB in children.

in which the immune system does not recognize or attack a disease target, until they grew older. “Young patients have an immune response against the virus that is better than adults that work to keep the level of virus down, but it is not sufficient to clear it,” Bertoletti said. Typically, adults show signs of liver damage after the age of 30, by which time their Tcells have become fatigued and are no longer performing optimally. Control rates for HBV drugs are about 20 percent. Cure rates are significantly lower, about 2-3 percent, Bertoletti said. Positive therapeutic effects are often temporary and viral levels increase once patients think the virus has cleared and stos taking medication. CHB infections can lead to cirrhosis of the liver, liver cancer and liver failure. “The implication is that young patients have an immune reaction against HBV, perhaps they should be monitored when they are young and not just when they become adults,” Bertoletti said. “It could be that treating patients when they are younger could yield a better response.”

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November 2012

Hepatitis

Hep C therapy just as effective for prisoners Elvira Manzano

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rison inmates infected with hepatitis C virus (HCV) are just as likely to benefit from cornerstone antiviral treatment with combination pegylated interferon (PEG-INF) and ribavirin as community patients, a recent US study has shown. In the study, rates of sustained viral response (SVR) did not differ between the two groups – 42.9 percent for incarcerated patients and 38 percent for non-incarcerated patients (P=0.304). [Hepatology 2012; DOI:10.1002/hep.25770] “Given that a history of intravenous drug use is more frequent among inmates, there is a higher prevalence of HCV infection in the prison population,” said lead study author Dr. Michael Lucey, chief of the Division of Gastroenterology and Hepatology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, US. “HCV treatment during incarceration provides an opportunity to make a significant improvement to public health.” Previous studies have shown that inmates were 156 times more likely to acquire hepatitis C, compared with at-risk individuals in the community. In the US, up to 31 percent of inmates have chronic hepatitis C infection compared with only 2 percent in the general population, yet inmates are among the most

difficult population to reach with critical health information and treatment. The researchers compared antiviral therapy between incarcerated and non-incarcerated patients at an academic center in the US between January 2002 and December 2007. Ninety-seven (out of 234) inmates achieved SVR compared with 115 (out of 319) in community patients. All patients in the study have non-genotype 1 virus and are not co-infected with HIV. The same number of patients from both groups completed full treatment. SVR, or undetectable HCV load in the blood 6 months after completion of treatment, is almost synonymous to a “cure.” Patients who achieve that status experience slower progression of liver disease, however, a portion of patients relapse shortly after therapy is stopped. “Our findings highlight the effectiveness of antiviral therapy in HCV-infected prisoners and show that it is as successful as treatment for HCV patients in the general population,” Lucey said. “A correctional setting may be an optimal setting for treatment that will help curb the hepatitis C public health crisis.” The research was funded by the American Cancer Society Research Scholar Grant and the National Institutes of Health.

35

November 2012

Research Reviews

ACE inhibitors, ARBs and pneumonia

I

t has been suggested that ACE inhibitors may protect against pneumonia. A systematic review and meta-analysis has been reported. Thirty-seven studies were included in the review. The risk of pneumonia was reduced significantly by 34 percent with use of ACE inhibitors compared with control treatment and by 31 percent compared with angiotensin receptor blockers (ARBs). ACE inhibitors seem to protect against pneumonia but ARBs do not. It is suggested that patients might try to continue with ACE inhibitor treatment despite a mild cough but an editorialist points to faults in the design of this study and disagrees with the suggestion given the uncertainty of present eviden ce.

Caldeira D et al. Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis. BMJ 2012;345:(Aug 4):15 (e4260); Barnes RA. Pneumonia and ACE inhibitors – and cough. Ibid: 6 (e4566) (editorial).

Maraviroc to prevent visceral GVHD

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hemokine (C-C motif) receptor 5 (CCR5) promotes lymphocyte recruitment to tissues involved in acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation and, in animal experiments, giving anti-CCR5 antibody protects against GVHD. Maraviroc is a non-competitive, slowly reversible small-molecule antagonist of CCR5. Now US researchers have shown that maraviroc may provide protection against GVHD. In vitro, maraviroc inhibited CCR5 internalization and lymphocyte chemotaxis but did not impair T-cell function or the formation of hematopoietic-cell colonies. Among 35 patients treated with oral maraviroc from 2 days before to 30 days after transplantation plus standard anti-GVHD prophylaxis,

the cumulative rate of grade II to IV acute GVHD was low (14.7 percent by day 100 and 23.6 percent by day 180). The cumulative incidence of grade III or IV GVHD by day 180 was only 5.9 percent, there being no liver or gut GVHD before day 100 and little before day 180. The rate of death without disease relapse at 1 year was 11.7 percent and rates of relapse or infection were not excessive. Serum from treated patients prevented CCR5 internalization by chemokine (C-C motif) receptor ligand 5 (CCL5) and blocked T-cell chemotaxis in vitro. Maraviroc shows promise as prophylaxis against visceral acute GVHD. Reshef R et al. Blockade of lymphocyte chemotaxis in visceral graftversus-host disease. NEJM 2012;367:135–45.

36

November 2012

Research Reviews

Reconstructive surgery for female genital mutilation

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n the last 10 years female genital mutilation (FMG) has affected 130-140 million girls worldwide, with 92 million in Africa. Now surgeons in France have reported the results of genital reconstructive surgery on 2,938 women between 1998 and 2009. The mean age at FMG was 6.1 years and the mutilative procedures had been performed mainly in Mali, Senegal, and the Ivory Coast, but 564 had been done in France. Reasons given for requesting reconstructive surgery were recovery of identity (99 percent), improvement in sex life (81 percent) and pain reduction (29 percent). Only 866 women (29 percent) attended the 1-year follow-up but most of them reported improvement in pain and sexual satisfaction. Women may benefit from reconstructive surgery after FMG. A multidisciplinary approach is needed to deal with nonsurgical issues. Foldès P et al. Reconstructive surgery after female genital mutilation: a prospective cohort study. Lancet 2012;380:134–41; Abdulcadir J et al. Reconstructive surgery for female genital mutilation. Ibid: 90–2 (comment).

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November 2012

Research Reviews

Racial differences in HIV infection in MSM

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lack men who have sex with men (MSM) make up about 1 percent of the US population, yet in 2009 nearly a quarter of all new HIV infections were in this group. A meta-analysis was conducted to explain the extent and causes of this disparity. The meta-analysis included 174 studies from the US, 7 from Canada and 13 from the UK. In all three countries, the rates of serodiscordant unprotected sex were similar in black MSM and other MSM. In the US and Canada, black MSM were less likely than other MSM to have a history of substance abuse. In the US and the UK, black MSM were more likely than other MSM to be HIV-positive, but HIV-positive black MSM in both countries were less likely than other HIV-positive men to start combination antiretroviral therapy (cART). In the US, black HIV-positive MSM were less likely than other HIV-positive MSM to have health insurance or a high CD4 cell count, to adhere to cART, or to be virally suppressed. US black MSM were more likely to report preventive behavior against HIV infection despite being twice as likely to have HIV risk factors such as unemployment, low income, previous imprisonment, and low level of education, compared with other US MSM. Racial differences in HIV and sexually transmitted infections and in cART initiation are common to the US and the UK. Millett GA et al. Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis. Lancet 2012;380:341–8; Koblin BA et al. Disparities in HIV/AIDS in black men who have sex with men. Ibid: 316–8 (comment).

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November 2012

Research Reviews

Antiretroviral prophylaxis for HIV-1-negative partner

A

study at nine centers in Kenya and Uganda has shown that antiretroviral prophylaxis given to the HIV-1-negative partner of an HIV-1-serodiscordant couple may prevent acquisition of the infection. The trial included a total of 4,747 serodiscordant heterosexual couples. The seronegative partners were randomized to tenofovir disoproxil fumarate (TDF) 300 mg daily, the same dose of TDF plus emtricitabine 200 mg daily (TDF-FTC), or placebo and followed up monthly for up to 36 months. The seropositive partners were not eligible for antiretroviral treatment on enrolment but were referred for treatment if they became eligible. During the study 82 seronegative partners became seropositive: 17 in the TDF group, 13 in the TDF-FTC group, and 52 in the placebo group, giving incidence rates of 0.65, 0.50, and 1.99 per 100 person–years, respectively. Both treatments were significantly better than placebo in both men and women but there was no significant difference between TDF and TDF-FTC. Adverse event rates were similar in the three groups. Both TDF and TDF-FTC were effective prophylaxis for the seronegative partner of HIV-1 serodiscordant heterosexual couples.

Baeten JM et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. NEJM 2012;367:399–410; Cohen MS, Baden LR. Preexposure prophylaxis for HIV-where do we go from here: Ibid: 459–61 (editorial); Abdool Karim SS et al. Preexposure prophylaxis for HIV prevention. Ibid: 462–5 (clinical decisions).

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November 2012

Research Reviews

Immunization against polio in Pakistan, Afghanistan

M

ore than one in three cases of poliomyelitis occurs in Pakistan, which may be the last country to interrupt transmission of the disease. In 2005, oral monovalent vaccines for poliomyelitis serotypes 1 and 3 were introduced because they are more immunogenic than the older oral trivalent vaccine (wild-type serotype 2 poliovirus was eliminated in 1999). A bivalent oral vaccine (serotypes 1 and 3) was introduced in Pakistan and Afghanistan in 2009–2010 after it had been shown to be as effective as the two monovalent vaccines. Vaccine programs in these countries have, however, been interrupted by war, security issues, cultural barriers and natural disasters, and the incidence of poliomyelitis has increased in both countries since 2008. A case-control study of children with acute flaccid paralysis in Pakistan and Afghanistan has provided data about the incidence of poliomyelitis and the effectiveness of vaccines. The study included 46,977 children aged up to14 years with acute flaccid paralysis in the years 2001 to 2011. Among these children there were 1,155 cases of poliomyelitis (poliovirus in stools). In Pakistan, there were 710 cases due to serotype 1 virus and 215 due to serotype 3. In Afghanistan, there were 173 type 1 cases and 56 type 3. The clinical effectiveness of a dose of oral vaccine against serotype 1 poliomyelitis was 12.5 percent for trivalent vaccine, 34.5 percent for monovalent vaccine, and 23.4 percent for bivalent vaccine. The bivalent vaccine was non-inferior to the monovalent vaccine. There was a fall in vaccination coverage during 2006–2011 in southern Afghanistan and in federally administered tribal areas Baluchistan and Khyber Pakhtunkhura in Pakistan. Despite the use of more effective vaccines the decreased vaccine coverage resulted in a lowering of vaccine-induced population immunity to serotype 1 poliovirus and an increased incidence of poliomyelitis. The use of bivalent oral poliomyelitis vaccine could eradicate serotype 1 poliomyelitis and minimize the risk of outbreaks of serotype 3 disease. Difficulties in vaccine coverage have limited program effectiveness in Pakistan and Afghanistan. O’Reilly KM et al.The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001-11: a retrospective analysis. Lancet 2012;380:491–8; Minor PD. Polio vaccines and the eradication of poliomyelitis. Ibid: 454–5 (comment).

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November 2012

Research Reviews

Antiretroviral prophylaxis for at-risk women

A

study in Kenya, South Africa, and Tanzania has assessed the prophylactic use of combined tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in women at increased risk of HIV-1 infection, with negative results. The trial included 2,120 sexually active HIV-negative women aged 18–35 years. Randomization was to TDF-FTC or placebo once daily for 52 weeks and follow-up was every 4 weeks for 60 weeks. HIV infection occurred in 33 women in the prophylaxis group and 35 in the placebo group (incidence 4.7 vs. 5.0 per 100 person–years, a nonsignificant difference). Prophylaxis was associated with higher rates of nausea,

vomiting and raised alanine amino-transferase levels. Drug discontinuation for kidney or liver function abnormalities was significantly more frequent in the TDF-FTC group (4.7 percent vs. 3.0 percent). Plasma drug level testing suggested that drug adherence was low. Prophylaxis with TDF-FTC was not effective in this study but rates of adherence were probably low. Van Damme L et al. Preexposure prophylaxis for HIV infection among African women. NEJM 2012;367:411–22; Cohen MS, Baden LR. Preexposure prophylaxis for HIV – where do we go from here? Ibid: 459–61 (editorial); Abdool Karim SS et al. Pre exposure prophylaxis for HIV prevention. Ibid: 462–5 (clinical decisions).

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November 2012

Research Reviews

Telehealth: Is it worthwhile?

T

he British government spent £30 million over 3.5 years on an evaluation of telehealth care for people with diabetes, chronic obstructive pulmonary disease (COPD) or heart failure. Government ministers have greeted the results with great enthusiasm but professional responses have been more muted. Recruitment to the study took place in 179 general practices in England between May 2008 and November 2009 and it included 3,230 patients. The general practices were randomized to telehealth or usual care for people with one of the three conditions. During the study, the proportion of patients admitted to hospital was 42.9 percent (telehealth) vs. 48.2 percent (controls), a difference that is statistically significant but of questionable clinical importance. Mortality was 4.6 percent vs. 8.3 percent, a statistically significant 46 percent proportional reduction with telehealth but only a 3.7 percent absolute reduction. There was, however, a saving of 59 lives among the 3,230 patients over 12 months. The rates of emergency admission (0.54 vs. 0.68 per patient) were not significantly different after adjustment for baseline characteristics. Hospital costs did not differ significantly between the two groups. There is a danger of too simplistic an interpretation of the results. It is not a matter of telehealth ‘working’ or ‘not working’ but of finding the place of the technology, its incorporation into care by patients and professionals, and its use for different problems and conditions. Politics should not leap ahead of sound professional assessment.

Steventon A et al. Effect of telehealth on use of secondary care and mortality: findings of the Whole System Demonstrator cluster randomised trial. BMJ 2012;345:(July 14):16 (344: e3874); Car J et al. Telehealth for long term conditions; Ibid: 7(344:e4201) (editorial); Gornall J. Does telemedicine deserve the green light? Ibid: 20–3(345:e4622) (Telehealth); Godlee F. Telehealth: only part of the solution. Ibid: 00(345:e4724) (editor’s choice).

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43

S

November 2012

After Hours

tanding atop St Paul’s Hill, facing the sea, you just need to close your eyes and get whisked away by the gentle breeze to a time not very long ago when Malacca was a bustling port with ships, sailors and traders from the far corners of the world. Nestled strategically between the Indian Ocean and the South China Sea, protected from winds, earthquakes and volcanoes, it is little wonder why Malacca was an international trading port. It is precisely because of Malacca’s status as an international harbor that so many pow-

ers tried to conquer it. Today, as one strolls through the streets of Malacca town, it is easy to spot the various influences of the colonists who came and went over the centuries. Of course, it helps that there are little plaques inserted into the walls, signs and fences to indicate when the structures were built and what they served as. At the foot of St Paul’s Hill, you can see A’ Famosa, the landmark fort that was built by the Portuguese. Also a remnant of those times is the chapel on St Paul’s Hill. In Malacca’s town square, the Stadthuys, easily distinguishable by its red walls, sits beside Christ

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November 2012

After Hours

Church, also built by the Dutch. In the town square, tourists mill around, snapping pictures of the red buildings as colorful trishaws wait for passengers. At the riverbank, one cannot ignore the large ship that appears to have docked there. The Malacca Maritime Museum is a replica of the Flora de La mar, a Portuguese trading vessel that sank off the coast of Malacca while en route to Portugal with loot plundered from Malacca. Inside, visitors can get a peek into the trading history of Malacca, from the time of the Sultanate and through the years of Portuguese, Dutch and British dominance. Malacca has turned some of its historic buildings into museums housing precious relics of its past. The Stadthuys, once a Dutch administrative building, now houses historical artifacts, guiding visitors through the history of Malacca from its humble beginnings to its height of glory as a trading destination and onwards through the years of colonization by the European powers.

Everything in Malacca is within walking distance. From the A’Famosa to the Stadthuys, it is just a few minutes’ walk. In between are many attractions for tourists to feast their eyes on. And right by the town square is the famed Jonker Street. Jonker Street is a delight for anyone who loves antiquities or just finds joy looking at curios. One of the shops is a cobbler’s, who still makes shoes worn by the ancient Chinese women with bound feet and authentic Nyonya beaded slippers. While wandering about these streets, you may also be ‘accosted’ by the wonderful smells of nyonya cuisine wafting from the little coffeeshops. The beauty and charm of Malacca must be experienced first-hand. Just a 2-hour drive from Kuala Lumpur, it’s the perfect place for a weekend getaway. With good food and a rich culture, one leaves Malacca feeling sated in both body and mind, already longing for another round of ayam pongteh and chicken rice balls.

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November 2012

After Hours

Crater culture Yen Yen Yip investigates the music and magic of Lake Toba in North Sumatra, Indonesia.

T

 he Batak man sits in front of a multihued display of souvenir T-shirts and ulos, the traditional cloth of North Sumatran Bataks. A two-stringed mandolin is cradled in his arms. He opens his mouth to sing and reveals a row of broken teeth. With one hand clasping, moving and pressing down on alternate string positions, he strums, coaxing a twanging melody out of the mandolin to accompany his hoarse voice. The song is harsh and strangely elemental; it conjures up images of men sitting around a fire at night, drinking palm fruit toddy after a day of fishing on Lake Toba. One of the most famous features of Lake Toba is a caldera – a crater lake that was formed when a super-volcano erupted more than 69,000 years ago. The eruption blew up about 2,800km3 of material and created a colossal hole about 906m above sea level, which gradually filled with water. Tens of thousands of years later, the Austronesian people traveled to Sumatra, made their way inland and found a beautiful lake ringed with forested dusky-blue silhouettes of mountains. The ones who settled on the surrounding mountainous regions and Samosir, the island in the middle of the lake, became known as the Toba Bataks. Accounts of Batak traditions date back to the 1200s. Some customs have survived the test of

time. For instance, traditional music played with Batak instruments such as the two-stringed mandolin, flute and drums is still used during ceremonies and festivities. At these events, ulos – cloth weaved with Batak designs – are folded lengthwise and draped over a shoulder. Some Bataks on Samosir continue to live in houses called rumah adat, built with distinctive roofs that sweep upwards on either end like buffalo horns, the gables adorned with elaborate carvings of thumbprint-like whorls and lines. Other tribal rituals, such as cannibalism, have died out. Early accounts of the Bataks’ predilection for human flesh came from the European explorer Marco Polo, who traveled to Sumatra in the 1290s and wrote about stories told to him of “man-eaters” who eat humans “stump and rump”. In the 1800s, Sir Stamford Raffles and other colonialists studied cannibalistic rituals of the Bataks and reported that human flesh was typically eaten when tribes waged war against neighboring villages and captured prisoners, or if a tribe member was accused of legal infringements such as murder, rape or theft. In Samosir, these grisly details can be recounted in full at Ambarita, a tribal village in Samosir which features a set of historic stone chairs where a judicial council would have sat to decide the fate of a

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November 2012

After Hours

prisoner. If the prisoner was condemned to execution, he would be beheaded; the body would be disposed in the lake, but the blood collected and the liver extracted for consumption. The Bataks believed that all humans possess a tondi, or a life-soul, which can affect his or her physical well-being: a weakened tondi can lead to illness and even death. The blood and the liver, considered to be rich in tondi, were consumed to heal and strengthen the eater’s spiritual self. In 1890, the Dutch colonial government passed a law banning cannibalism. Rumors of cannibalism among the Bataks persisted until the early 20th century. Today’s Toba Bataks have mostly converted to Christianity. Brightly colored churches with steeples glinting in the sun are frequently spotted in the middle of rice paddies and agricultural fields along the dusty, empty roads of Samosir. Before the advent of Christianity, however, the Batak religious worldview was animistic. Divination and magic were commonly practised. Datuks – animistic shamans – recorded magic spells, healing charms, prophecies and other mystical notes in arcane Batak characters on pushtahas, books made of tree bark, folded and opened in concertina style. Certain burial practices have endured until today. At death, the Bataks are buried twice. It was traditionally believed that the tondi of a deceased person will vanish from the body; however, the begu, or the death-soul, remains. A priest is required to perform rituals at the first funeral to advise the begu to leave the family and the village. Reburial typically takes place about 8 years after death, during

which the bones are exhumed and cleaned, to be reinterred in a bone house that is elevated above ground to be closer to the heavens. The tomb of the Batak rajah Sidabutar rests on a hill in Tomok, a village in southern Samosir, past about half a kilometre of souvenir stalls lining a narrow meandering lane. His sarcophagus is carved in stone and sits out in the sun, bleached and silent. Legend has it that the monarch was a just and wise ruler whose affections were spurned by a Batak beauty, Anting Malela. In vengeance, the rajah cursed the woman and drove her insane through black magic. The rajah’s unrequited love persisted at his deathbed: he had a statue of Anting Malela carved to adorn his tomb. Today, the sarcophagus is the object of tourist fascination and camera clicks.

Getting There Lake Toba is a five hour drive from Medan, the largest city in North Sumatra. Tourists can fly in to Medan through Polonia International Airport.

What to Do • D  ive into the delicious cool waters of the crater lake • Dance with the locals in a traditional Batak performance • Hike the peaceful, rolling hills of Samosir and drink in the scenery • Take a sip of palm fruit toddy

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November 2012

Humor

“Give it to me straight doctor, should I start dating?”

“He likes his steak and mashed potatoes intravenously!”

“At our hospital we either perform a Cesarian, or the Heimlich maneuver. Which one do you prefer?”

“This here? I cut myself shaving!”

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

“I didn’t expect to still be constipated up here!”

“I wouldn't worry about it. He won't get far without lungs!”

48 November 2012 Calendar November

December

2012 Scientific Sessions of the American Heart Association 3/11/2012 to 7/11/2012

National Diagnostic Imaging Symposium 2/12/2012 to 6/12/2012

Location: Los Angeles, California, US Info: American Heart Association Tel: (1) 214 570 5935 Email: [email protected] Website: www.scientificsessions.org

Location: Orlando, Florida, US Info: World Class CME Tel: (980) 819 5095 Email: [email protected] Website: www.cvent.com/events/national-diagnostic-imaging-symposium-2012/event-summary-d9ca77152935404ebf0404a0898e13e9.aspx

8th International Symposium on Respiratory Diseases & ATS in China Forum 2012 9/11/2012 to 11/11/2012

Asian Pacific Digestive Week 2012 5/12/2012 to 8/12/2012

Location: Shanghai, China Info: UBM Medica Shanghai Ltd. Tel: (86) 21-6157 3888 Extn: 3861/62/64/65 Fax: (86) 21-6157 3899 Email: [email protected] Website: www.isrd.org

3rd Annual Meeting of the American Association 6 for the Study of Liver Diseases 9/11/2012 to 13/11/2012 Location: Boston, Massachusetts, US Info: American Association for the Study of Liver Diseases Tel: (1) 703 299 9766 Website: www.aasld.org

9th International Diabetes Federation-West Pacific Region Congress 25/11/2012 to 27/11/2012 Location: Kyoto, Japan Info: Japan Convention Services, Inc. Tel: (81) 6 6221 5931 Fax: (81) 6 6221 5939 E-mail: [email protected] Website: www2.convention.co.jp/idfwpr2012

Location: Bangkok, Thailand Tel: (66) 2 748 7881 ext. 111 Fax: (66) 2 748 7880 E-mail: [email protected] Website: www.apdw2012.org

World Allergy Organization International Scientific Conference (WISC 2012) 6/12/2012 to 9/12/2012 Location: Hyderabad, India Info: World Allergy Organization Tel: (1) 414 276 1791 Fax: (1) 414 276 3349 E-mail: [email protected] Website: www.worldallergy.org

54th American Society of Hematology Annual Meeting 8/12/2012 to 11/12/2012 Location: Georgia, Atlanta, US Info: American Society of Hematology Tel: (1) 202 776 0544 Fax: (1) 202 776 0545 Website: www.hematology.org

17th Congress of the Asian Pacific Society of Respirology 14/12/2012 to 16/12/2012 Location: Hong Kong Info: UBM Medica Pacific Limited Tel: (852) 2155 8557 Fax: (852) 2559 6910 E-mail: [email protected] Website: www.apsr2012.org

49 November 2012 Calendar Upcoming 16th Bangkok International Symposium on HIV Medicine 16/1/2013 to 18/1/2013 Location: Bangkok, Thailand Info: Ms. Jeerakan Janhom (Secretariat) Tel: (66) 2 652 3040 Ext. 102 Fax: (66) 2 254 7574 E-mail: [email protected] Website: www.hivnat.org/bangkoksymposium

28th Congress of the Asia-Pacific Academy of Ophthalmology 17/1/2013 to 20/1/2013 Location: Hyderabad, India Info: APAO Secretariat Tel: (852) 3943 5827 Fax: (852) 2715 9490 Email: [email protected] Website: www.apaoindia2013.org

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

Asian Pacific Society of Cardiology 2013 Congress 21/2/2013 to 24/2/2013 Location: Pattaya, Thailand Info: Kenes Asia (Thailand Office) Tel: (66) 2 748-7881 Fax: (66) 2 748-7880 Email: [email protected] Website: www2.kenes.com/apsc2013/pages/home.aspx

23rd Conference of the Asia Pacific Association for the Study of the Liver 7/3/2013 to 10/3/2013 Location: Singapore Info: Gastroenterological Society of Singapore, The Asian Pacific Association for the Study of the Liver Tel: (65) 6292 4710 Fax: (65) 6292 4721 Email: [email protected] Website: www.apaslconference.org

62nd American College of Cardiology (ACC) Annual Scientific Session 9/3/2013 to 11/3/2013 Location: San Francisco, California, US Info: American College of Cardiology Foundation Tel: (415) 800 699 5113 Email: [email protected] Website: www.accscientificsession.org/Pages/home.aspx

4th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association 27/3/2013 to 30/3/2013 Location: Shanghai, China Info: Asian Pacific Hepato-Pancreato-Biliary Association Tel: (86) 21 350 30066 Fax: (86) 21 655 62400 Email: [email protected] Website: www.aphpba2013shanghai.org/

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