MEDICAL TRIBUNE NOVEMBER 2012

November 2012

Vaccination the key to global health

FORUM

Managing HFMD in primary care

IN PRACTICE

Step-off approach to LABA asthma therapy under scrutiny

Manfaat tanaman Phyllanthus niruri dan Vitis vinifera

INDONESIA FOCUS

Metformin can be used more widely

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3 November 2012

Step-off approach to LABA asthma therapy under scrutinyElvira Manzano

The approach of discontinuing long-act-ing β2-agonist (LABA) therapy (‘step-off’ 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 con-trolled trials comparing step-off therapy with continued use of LABA and inhaled ICS medi-cations found that the LABA step-off approach was linked to a rise in asthma-related impair-ment. Compared with patients who contin-ued 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-signifi-cant 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 LA-BAs 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 conduct-ing 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 contin-ued use of LABAs,” said Brozek.

Brozek and his fellow investigators cau-tioned 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 accompa-nying commentary.

Moreover, they called on the FDA to recon-sider 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.”

4 November 2012

Alexandra Kirsten

Celebrities 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 ex-

perts, unlike many health experts, they “of-ten 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 Medi-cal 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 evi-dence-based health policy reform.

Talking about the case of Australian crick-eter 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 en-gagement and need to be realistic about the need to sustaining public campaigns beyond their first burst.”

When photographs appeared of the sports-man 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 false-positive 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 engage-ment 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 influenc-es 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 so-ciety, even in politics. Rather than relying on media stunts, modern health campaign-ers “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 in-volved. That’s a lie too”, Rayner concluded.

Do celebrities help public health campaigns?

5 November 2012 Forum

Vaccination the key to global healthExcerpted 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.

It has been shown by historical studies that there is a relationship between health and wealth, and that it really pays for govern-

ments to invest in health. Because of the dual relationship, there is a double dividend, espe-cially in low- and middle-income countries. The reason is that healthy populations lead to economic growth.

When people remain healthy, they also de-velop better physical and cognitive capabili-ties, so that in adulthood they become more energetic and active workers, which leads to higher incomes for their families, higher pro-ductivity and greater output, which is mea-sured as gross domestic product (GDP) for the government.

It is beneficial investing in health preventa-tive measures that do not cost much or preven-tative 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 work-ing well. If children are healthy, it’s better for the families because they will be able to de-velop 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-of-pocket 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 pro-ductivity and, as a consequence, its income.

One measure to express health is life expec-tancy. Health can be defined in many ways, so epidemiologists and economists as well have taken one common measure, which is life ex-pectancy, to express the benefits that accrue in a healthy population.

Life expectancy is a measure at the popula-tion level – it’s an average among all individu-als that survive in society. So, if large numbers of children die prematurely, the life expectan-cy 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-

Health can be defined in many ways...‘‘

6 November 2012 Forumsures 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 es-tablish 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 infrastruc-ture 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 stud-ies that have been done, the global commu-nity has recognized that vaccination is one of the world’s most important and cost-effective health interventions, with positive socioeco-nomic effects on society. [World Economics 2005;6:15-39]

Key stakeholder benefits of vaccination in-clude 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 inter-est 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 commu-nity, 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 ap-proximately 20 diseases through vaccination

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

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 lat-er 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 Im-munisation (GAVI) was founded in 2000 to fund vaccines in very poor countries that can-not afford any immunization programs or expand it with newer vaccines, and are also lacking a proper health infrastructure to pro-vide vaccines to children in rural areas.

The GAVI Alliance is a public-private part-nership built on international solidarity and it devised a very innovative way of financing through donor fronts from a number of coun-

...vaccination is one of the world’s most important and

cost-effective health interventions

‘‘

7 November 2012 Forumtries and foundations including the Bill & Me-linda 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 coun-tries with incomes below US$1,500 per person per year to give them an incentive to start de-veloping their programs.

Through the GAVI Alliance, rigorous gov-ernment policies, and strengthening of vac-cination 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-re-ports/ 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 immuniza-tion programs.

To be able to compare with other studies and to compare between diseases, the WHO has come up with a metrics called DALY (dis-ability-adjusted life years), which is a mea-surement 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 gov-ernments adopting the hepatitis B, pneu-mococcal and Haemophilus influenzae type B childhood vaccines.

Investing in vaccination gives a high return in the short- and long-term for both individu-als 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?

8 Indonesia FocusNovember 2012

S alah satu topik pada ‘American Acad-emy 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 dikolaborasi-kan dengan Kementerian Kesehatan dan Ke-menterian 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 ter-hadap kanker payudara. “Riset meng-gunakan ekstrak kasar, karena ekstrak kasar tidak terlalu toksik dan persia-pannya lebih sederhana. Namun masih banyak tantangan ke depan untuk men-getahui 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 me-miliki reseptor dan protein yang spesi-fik 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 mul-tipel 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 se-cara multipel,“ tukas Prof. Nurhalim.

Pakar biomolekuler dari Universitas Padjajaran ini telah menemukan beber-apa 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-

Manfaat tanaman Phyllanthus niruri dan Vitis viniferaHardini Arivianti

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


tition (c-myc) dan cell senescence/non-di-viding (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%, se-dangkan ekstrak kasar mencapai 92%. Ini merupakan kesempatan besar un-tuk 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 dik-eringkan dan diekstrak dengan etanol lalu dikeringkan hingga kadar air sangat minim. Rencana ke depan akan diker-ingkan 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 men-garah ke uji klinis yang rencananya akan kami lakukan tahun depan.”

Uji klinis yang akan dilakukan meneli-ti 2 hal, yaitu meniran (tunggal) dan me-niran + biji anggur (gabungan). Secara tunggal, meniran dapat memicu perbai-kan DNA dan bermanfaat dalam antiag-ing. 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.


P 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) bersa-ma Dr. Eilardus Koen (Eiko) de Jong (‘Nu-tritional and Clinical Trial Monitor’ dari FrieslandCampina), beberapa waktu lalu memaparkan hasil studi klinis lanjutan isomaltulosa.

Studi pertama isomaltulosa telah di-lakukan 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 perha-tian (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 perkem-bangan 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 motiva-si, self-esteem, decision making, komitmen. Otak berinteraksi dengan lingkungan yang dapat berupa penyakit infeksi, nu-trisi, imunitas, orang-orang dan keluarga, sensasi serta edukasi dan pelatihan.

”Guna mendukung perkembangan fungsi kognitif, anak tidak hanya memer-lukan nutrisi tetapi juga perlu stimulasi,” tukas dr. Saptawati. Sebuah penelitian pada anak yang tidak diberi suplementasi zat gizi dan tidak distimulasi, menunjuk-kan 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 su-dah diberikan suplementasi zat besi, fungsi kognitif pada anak yang anemia tetap tidak bisa mengejar anak-anak yang tidak ane-mia. Hal ini menjadi dasar perlunya pence-gahan kekurangan zat besi pada anak.

Selanjutnya Dr. Saptawati memapar-kan, susu sangat superior karena sarat dengan zat gizi, protein, vitamin, mineral dan kalori, kecuali vitamin C. Walau kan-dungan kalori dan zat gizinya sama, susu yang diperkaya akan lebih baik diband-ingkan dengan susu biasa. “Anak harus mendapatkan makanan lengkap, seperti salah satunya adalah susu, agar dapat

Studi klinis lanjutan isomaltulosaHardini Arivianti

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


mendapatkan manfaat dari zat-zat gizi yang terkandung di dalamnya sehingga perkembangan kognitif anak tetap terjaga hingga usia dewasa,” jelas dr. Saptawati.

Studi lanjutanSetelah studi klinis pertama,

FrieslandCampina kembali melakukan studi klinis lanjutan yang dilakukan se-cara acak pada 127 anak usia 5-6 tahun selama rentang waktu 3 bulan guna men-getahui konsistensi manfaat isomaltulosa terhadap kinerja kognitif anak. Subyek dibagi menjadi 4 kelompok yang diberi-kan 4 produk susu dengan susu pertum-buhan 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 parti-sipan yang lebih banyak dan rentang wak-tu yang lebih lama. Hasil temuan secara signifikan mengungkapkan isomaltulosa dalam susu pertumbuhan berpengaruh positif terhadap parameter ingatan dan perhatian dibandingkan dengan susu per-tumbuhan standar.

“Dari beberapa studi atau penelitian, disimpulkan isomaltulosa merupakan je-

nis karbohidrat yang menghasilkan glu-kosa yang memberikan energi lebih lama untuk otak. Ini sangat penting mengin-gat otak membutuhkan energi yang ter-us menerus sehingga suplementasi iso-maltulosa menjadikan atensi dan memori pada anak lebih baik,” jelas Dr. Eiko.

Mengenai studi lanjutan ini, Dr. Sap-tawati menambahkan, instrumen yang di-gunakan berasal dari Amsterdam dan in-gin mempertegas hasil studi sebelumnya dan ternyata dengan instrumen yang ber-beda, menunjukkan hasil yang sama atau konsisten.

Selaku Spesialis Psikiatri Anak, dr. Tjhin memaparkan studi lanjutan ini sudah se-lesai dilakukan tahun 2011 lalu. Pengujian dilakukan terhadap kemampuan mengin-gat anak setelah melihat sederetan gam-bar dan mengulangnya. Hasilnya menun-jukkan jumlah gambar yang lebih banyak dan waktu yang lebih cepat pada kelom-pok 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. Den-gan alat ini diketahui kemampuan mem-pertahankan konsentrasi ternyata lebih panjang.


Jangan abaikan kelenjar tiroid

Karsinoma tiroid merupakan penyakit keganasan sistem endokrin yang pal-ing sering ditemukan. Kira-kira 10-

20% 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 dite-mukan nodul di dalamnya. Sekitar 4-8% no-dul tiroid bisa ditemukan saat palpasi dae-rah 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 ma-salah keganasan pada kelenjar tiroid memi-liki prognosis dan progresivitas yang lambat. Sesuai data RSCM selama 18 tahun, mencatat angka survival mencapai 75%. Hal ini diung-kapkan oleh Prof.dr. Johan S Masjhur, SpPD-KEMD, SpKN.

Karsinoma tiroid dibagi menjadi 3 jenis yaitu berdiferensiasi baik (karsinoma tiroid papilifer/KTP, karsinoma tiroid folikuler/KTF, dan karsinoma sel Huthle), berdiferensiasi se-dang dan tak terdiresensiasi (anaplastik). In-sidensi 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 ti-roid tipe folikuler dan anaplastik lebih tinggi, terutama pada usia lanjut. Pada daerah yang kaya akan yodium (Irlandia), yang lebih me-nonjol adalah tipe papuler.

Gambaran klinis berupa nodul tunggal (70-75%), sesak napas, perubahan suara, su-lit menelan, dan pembesaran kelenjar getah

bening di leher. Insidensi kanker ini dipen-garuhi oleh beberapa faktor yaitu demografi, lingkungan, usia, riwayat keluarga dan ter-papar radiasi. Untuk mencegah keterlamba-tan terapi kanker ini memerlukan modalitas pemeriksaan karena tidak ada gambaran kli-nis yang khas.

”Sekitar 80-90% penderita kelainan kelen-jar tiroid adalah perempuan. Namun, persen-tase 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 ber-beda. 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 dila-kukan pengelolaan terpadu. Pertama perlu dilakukan pemeriksaan laboratorium untuk mengetahui fungsi kelenjar tiroid dan petan-da tumor yaitu memeriksa TSH, T3, T4, tiro-globulin dan kalsitonin serta foto polos bagian leher. Kedua, dengan biopsi jarum halus.

Selain itu tindakan yang dilakukan bisa be-rupa operatif dan non-operatif. Operatif men-cakup bedah terapetik bersifat ablasif berupa tiroidektomi total, tiroidektomi sub total, ti-roidektomi mendekati total, lobektomi total, subtotal lobektomi dan ismolobektomi.

Tindakan non-operatif berupa radioterapi, kemoterapi dan terapi hormonal dalam ben-

Hardini Arivianti


tuk suplementasi. Pada kondisi pasien tidak lagi memiliki kelenjar tiroid (kondisi hipotiro-id) 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 ber-sifat ganas,” jelas Prof. Johan. Pada peme-riksaan USG tanda-tanda karsinoma melip-uti 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 den-gan 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 me-rupakan 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 reku-rensi. Prognosis dikaitkan dengan usia, bila usia > 60 tahun maka tingkat rekurensi dan kematian lebih tinggi. Tipe papiler memiliki angka survival yang lebih tinggi dibanding-kan tipe folikuler. Faktor prognostik yang sangat penting bagi penderita kanker tiroid adalah ukuran tumor dan kadar Tg 1 bulan pasca operasi.

Update seputar GOLD Guideline

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

Hardini Arivianti

Pada ‘International Meeting on Respiratory Care Indonesia’ (RESPINA) ke-14 yang

berlangsung tanggal 3-6 Oktober 2012 lalu, ‘Chronic Obstructive Pulmonary Disease’ (Pe-nyakit Paru Obstruktif Kronik/PPOK) menjadi salah satu bahasan utama. “Penyakit paru ini akan semakin banyak kasusnya yang diaki-batkan 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, pe-nyakit 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 disebab-kan oleh keterbatasan aliran darah yang bersi-fat progresif akibat inflamasi kronik. Perlu diperhatikan pada PPOK (menurut revisi


GOLD) adalah faktor eksaserbasi dan komor-biditas yang memiliki peran dalam perjalanan PPOK secara keseluruhan dan dapat memper-berat 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 didasar-kan 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 uda-ra yang persisten atau PPOK.”

Selanjutnya, Prof. Faisal memaparkan pent-ingnya penilaian pada PPOK. “Penilaian ini harus dilakukan guna menentukan tatalak-sana, prognosis dan menentukan apa yang akan dilakukan dokter terhadap pasiennya.” Penilaian PPOK mencakup 4 hal yaitu gejala, derajat keterbatasan aliran udara, risiko eksas-erbasi 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 (se-sak napas saat melakukan strenous exercise), 1 (sesak napas saat berjalan cepat di tempat da-tar 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 me-narik napas setelah berjalan kira-kira 10 meter atau setelah berjalan kaki beberapa menit pada tempat datar), dan 4 (tidak bisa pergi kemana-mana 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 terapiMenurut revisi atau tambahan pada guide-

line GOLD, penilaian terhadap eksaserbasi juga perlu dilakukan. Dibedakan, < 2x dalam setahun atau ≥ 2x setahun dan dilihat juga ni-lai FEV1 < 50% dari nilai prediksi. “Eksaserbasi menjadi penting karena merupakan kondisi akut PPOK yang ditandai perburukan gejala-gejala (pertambahan batuk, produksi sputum, sesak) dan meningkat dibandingkan hari ke hari serta biasanya memerlukan obat lain (an-tibiotik atau kortikosteroid),” papar Prof. Fais-al. Esksaserbasi dapat dipicu oleh beberapa faktor, yaitu infeksi virus pada saluran napas bagian atas (50%) dan dan faktor lain, misal-nya 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 ge-jala 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 menu-runkan kematian akibat PPOK.

Selanjutnya Prof. Faisal Yunus menjelas-kan mengenai guideline GOLD 2009 yang me-nilai hanya dari spirometri, dan GOLD 2011 tidak lagi hanya dari spirometri namun juga


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 ber-henti merokok dan dilanjutkan dengan pem-berian obat-obatan. Sesuai rekomendasi far-makoterapi GOLD 2011, pada PPOK yang stabil terapi utama dapat diberikan beta A2

agonis dan antikolinergik kerja lama. Bisa dit-ambahkan inhalasi kortikosteroid.

Revisi guideline GOLD 2011 disimpulkan oleh Prof Faisal sebagai berikut spirometri di-perlukan 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 di-berikan.

Paisen Karakteristik Klasifikasispirometri Eksaserbasi/tahun mMRC CAT

A Risikorendah,gejalakurang GOLD1-2 ≤ 1 0-1 <10

B Risikorendah,gejalabanyak GOLD1-2 ≤ 1 2+ ≥10

C Risiko tinggi, gejala kurang GOLD 3-4 2+ 0-1 <10

D Risikotinggi,gejalalebihbanyak GOLD3-4 2+ 2+ ≥10

Indonesia meraih penghargaan Dr. GuislainHardini Arivianti

Bagus Utomo dari Indonesia terpilih sebagai pemenang pertama Penghar-gaan Dr. Guislain ‘Breaking the Chains

of Stigma’ untuk upayanya yang tidak men-genal lelah memberikan pemahaman guna memerangi stigma skizofrenia, melalui or-ganisasinya Komunitas Peduli Skizofrenia Indonesia (KPSI). Program Penghargaan Dr. Guislain ini merupakan penghargaan dunia berupa proyek kerja sama antara Museum Dr Guislain dan Janssen Research & Devel-opment, 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 Uni-versitas 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 men-jadi wadah untuk berbagi pengalaman bagi para pasien dan keluarganya. Saat ini KSPI memiliki 6400 anggota dari berbagai daerah dan aktif melakukan edukasi kepada ma-syarakat.

Perlu secara holistik“Penyebab gangguan jiwa adalah multi-


faktorial, yang dapat berupa faktor genetik, organobiologik, sosiokultural, psikologi, dan lain sebagainya,” tukas dr.Tun Kurnia-sih Bastaman, SpKJ dalam acara berkaitan dengan penghargaan Dr.Guislain kepada Bagus Utomo beberapa waktu lalu.

Sesuai Riskesdas (2007), mayoritas gang-guan 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 beri-kut: DKI Jakarta 2,03%, Aceh 1,85%, Suma-tera 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 skizo-frenia di Indonesia sekitar 0,46%, yang me-mang prosentasenya kecil namun dampak terhadap pasien dan keluarganya sangat be-sar” lanjutnya.

Penatalaksanaan tidak hanya memerlu-kan obat-obatan saja, lanjut dr. Tun, namun juga perlu hal lain misalnya psikoterapi, ke-giatan 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%). Kemungki-nan pemulihan maksimum tergantung kon-sistensi. Sekitar 75% pasien kambuh dalam waktu 1-1,5 tahun jika obat antipsikotik dihentikan atau tidak dikonsumsi teratur. Diperkirakan hanya sekitar 25% pasien den-gan skizofrenia yang mengonsumsi obat se-cara teratur.

“Kriteria sembuh bagi skizofrenia adalah bisa kembali berfungsi (pekerjaan, sos-ial, dll), dan diperkirakan sekitar 75-80% pasien dapat kembali berfungsi dan sekitar 25% akan terus mengalami kekambuhan. Kekambuhan ini biasanya terjadi akibat pu-tus obat.”

Terapi antipsikotik berupa oral dan injek-si 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, berja-lan seperti robot, dll. “Untuk menetralisir efek samping yang timbul secara individual ini dapat diberikan triheksipenidil (THP),” jelasnya.

Mengenai lini pertama terapi skizofre-nia, dr. Tun menjelaskan sedikit, sebenarnya kami sudah beralih ke generasi kedua yang efek sampingnya lebih ringan, dan sebagai lini pertamanya adalah risperidon.


Hardini Arivianti

Artritis rematoid (AR) secara pasti belum diketahui penyebabnya hing-ga 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 mem-bantu memperbaiki kualitas hidup pasien.

Berbagai studi pengobatan AR‘Indonesian Rheumatology Association’

(IRA) dan Roche Indonesia melakukan studi klinis tocilizumab PICTURE INA, yang me-libatkan 39 pasien dengan AR selama peri-ode Februari (2010)-Januari (2012). Studi ini dipimpin dr. Bambang Setyohadi, SpPD-KR yang dilakukan di lima pusat studi yaitu RSCM (Jakarta), RS Hasan Sadikin (Ban-dung), RS Dr Sardjito (Yogyakarta), RS Dr Soetomo (Surabaya), dan RS Saiful Anwar (Malang).

Hasil studi menunjukkan, tingkat remi-si pasien yang mendapatkan tocilizumab mencapai 85% dengan efek samping serius < 5%. Indikator remisi dinilai dengan meng-gunakan ’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 Investiga-tor’ studi klinis di Indonesia, Prof. Dr. dr. Handono Kalim, SpPD-KR menjelaskan studi itu menunjukkan manfaat tocilizumab bagi pasien AR sehingga dapat memberikan

Tocilizumab, harapan baru artritis rematoid

harapan baru dan memperbaiki kualitas hid-up pasien nantinya.

Menyusul studi PICTURE-INA, saat ini tengah berlangsung studi post marketing to-cilizumab, yaitu studi ACT UP dengan sent-er 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, SpPD-KR.

Sepak terjang IL-6Pengobatan AR diarahkan atas dasar me-

kanisme terjadinya penyakit ini yang salah satunya adalah mediator peradangan IL-6 (interleukin 6). Tocilizumab adalah peng-hambat antibodi monoklonal IL-6. Penelitian menunjukkan, terjadi peningkatan kadar IL-6 pada pasien AR. IL-6 merupakan media-tor peradangan yang paling banyak ditemu-kan 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 meng-ganggu proses penyerapan zat besi dari makanan dan pelepasan zat besi dari simpa-nan di makrofag. Anemia berkaitan dengan kelelahan, dan sekitar 30% pasien menderita anemia. IL-6 merupakan stimulator utama protein C reaktif (CRP) yang merupakan


indikator inflamasi kuat. Kadar CRP tinggi berkaitan dengan penyakit kardiovaskular.

Mengenal AR

Penyakit ini merupakan penyakit autoimun progresif dan sistemik yang ditandai oleh per-adangan kronis sendi tangan dan kekakuan, disertai gejala-gejala sistemik berupa kelelah-an, anemia, dan depresi. Peradangan menye-babkan 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 Menu-lar, DirJen Pengendalian Penyakit dan Penye-hatan 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 ta-hun sekitar 0,1-0,3% dan < 18 tahun menca-pai 1/100.000 orang. Banyak pasien yang ga-gal diterapi dengan terapi yang ada sekarang dan sekitar 30-40% pasien tidak mendapat-kan kontrol penyakit RA dari terapi yang ada sekarang serta > 50% tidak mencapai remisi penyakit (DAS28 ≤ 2,6).

Pengobatan ARTocilizumab 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 peng-hambat reseptor IL-6 bekerja dengan cara mengganggu jalur sinyal IL-6 dengan mengi-kat kedua reseptor IL-6 yang terlarut dalam darah dan yang terdapat di membran sel.

Pengobatan ditujukan untuk tercapainya remisi dengan cara mengurangi nyeri, men-gurangi inflamasi, menghentikan kerusakan sendi, memperbaiki fungsi sendi, dan mem-buat pasien nyaman. Pengobatan saat ini di-lakukan dengan dua cara, yaitu untuk men-gurangi rasa sakit dan pembengkakan pada sendi dengan menggunakan NSAID (Non Steroid Anti Inflammatory Drug) atau pred-nison dosis rendah. Sedangkan pengobatan lain adalah memperlambat atau mencegah proses penyakit dengan menggunakan ‘Dis-ease Modifying Arthritis Rheumatoid Drug’ (DMARD) yaitu DMARD tradisional misal-nya metotreksat, atau DMARD Biologis mi-salnya TNF Inhibitor, Rituximab, atau Tocili-zumab.

Penelitian juga menunjukkan, se-bagai monoterapi, tocilizumab lebih superior dibandingkan monoterapi dengan metotrek-sat. Efikasi tocilizumab juga lebih baik saat dibandingkan dengan obat biologi lain se-perti rituksimab, penghambat TNF-alfa, dan etanercept.

Dengan hasil positif terapi tocilizumab, tentu pilihan terapi pasien RA yang mem-berikan 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 ditera-pi dengan DMARDs terlebih dahulu. Jika dalam waktu 2-3 bulan tidak ada perbaikan, baru digunakan obat biologi.


Hardini Arivianti

Tema simposium “The Importance of Early Life Nutrition: Blue Print of Leg-

acy of Long Term Health” beberapa waktu lalu membahas pentingnya pemenuhan gizi anak di Indonesia, karena permasalahan be-ban ganda gizi (kekurangan dan kelebihan gizi) masih dihadapi Indonesia. Simposium ini diadakan oleh Perkumpulan Obsteri dan Ginekologi Indonesia (POGI) dan PT Nutri-cia Indonesia.

Sesuai data Riset Kesehatan Dasar (RISK-ESDAS) 2010, jumlah anak dengan berat badan kurang (wasting) dan pendek (stunt-ing) 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 pal-ing efektif yaitu harus dimulai sebelum masa kehamilan dan difokuskan pada 12 minggu pertama kehamilan karena inilah masa ter-penting dalam pembentukan cetak biru ge-netik sebagai penentu kesehatan anak hing-ga 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-

Perlunya pemenuhan gizi anak

lian dan kelainan poligenik. Pada periode perawatan antenatal, dokter perlu menan-yakan riwayat kesehatan keluarga, minimal 3 generasi. Kromosom abnormal dapat ter-jadi pada ibu berusia > 35 tahun, seromarker abnormal, ada riwayat kromosom abnormal pada anak pertama dan orang tua, serta rekurensi abortus spontan. Kelainan Mende-lian terjadi bila kedua orang tua merupakan carrier gen resesif otosom abnormal yang sama, usia orang tua > 50 tahun, dan tergan-tung jenisnya (otosomal, x-linked recessive/dominant), contohnya kistik fibrosis, hemofil-ia A, hiperplasia adrenal kongenital, dll. Ke-lainan 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 ti-dak akan tahu.

Penilaian antropometri mudah dan mu-rah, namun kerugiannya tidak bisa mende-teksi defisiensi protein, mikronutrien. Untuk lemak tubuh diukur dari cadangan lemak pada inter/intramuskular, sekitar organ dan saluran cerna, subkutan dan sumsum tu-lang, jaringan sarat pusat, dll. Olahragawan dan non-olahragawan, memiliki lemak tu-buh yang berbeda walau berat badan sama. Pada ibu dengan kifosis, agak sulit mengu-kur tinggi badan, sehingga dilakukan den-


gan teknik lain misalnya mengukur panjang tangan. Pengukuran antropometri juga men-gukur lingkar lengan atas, ketebalan lipatan kulit, rasio lingkar pinggang dan panggul, serta lebar siku. “Sub-scapula skinfold thick-ness (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 se-dikit, jadi sebaiknya tidak hanya melihat angka tetapi juga perhatikan kondisinya. Di-katakan dr. Damar, gabungan BMI dan skin-fold 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, menan-dakan komposisi lemak subkutannya tinggi. Selanjutnya, lingkar lengan atas dapat men-gukur komposisi massa otot tubuh dan cadangan protein.

Pengukuran status mineral dan trace ele-ments, misalnya zat besi, perlu dinilai taha-pannya. Tahap pertama defisiensi zat besi dapat dinilai dari kadar serum atau feritin plasma, dan tahap ke-2 dapat dilihat dari ka-dar zat besi serum, iron binding capacity serum dan plasma total, protoporfirin eritrosit dan serum transferrin receptor. Sedangkan tahap ke-3 dapat diukur dari hemoglobin, hema-tokrit dan eritrosit.

Selain itu, pemeriksaan yang tidak kalah penting adalah pemeriksaan klinis melalui anamnesa riwayat kesehatan ibu. Dijelas-kan oleh dr. Damar, pemeriksaan laborato-rium memiliki confounding effect. Bila hasil menunjukkan penurunan kadar retinol se-rum, berarti kemungkinan ada infeksi berat. Penurunan kadar vitamin E plasma juga bisa menandakan kemungkinan ibu mengalami infeksi seperti malaria, begitu pula bila ter-jadi penurunan pada kadar feritin (serum). Kadar zink plasma yang menurun menan-dakan kemungkinan ibu mengalami infeksi akut dan kronik.


Local events calendar21st Jakarta Diabetes MeetingJakarta, 10-11 November 2012Mercure Convention Centre Ancol, JakartaSekr : Divisi Endokrinologi dan Metabolisme, Fakultas Kedokteran Universitas Indonesia, RS Cipto Mangunkusumo, JakartaTel : 021-3907703, 3100075Fax : 021-3928658, 3928659Email : [email protected] : jakartadiabetesmeeting.com

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

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

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

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

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

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

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

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

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

22 November 2012 In Pract ice

Managing HFMD in primary care

Hand, 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 play-ground, 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 constant-ly 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 pre-vent the spread of infection. Simple messages teaching parents and children the proper way to wash their hands is an effective method of preventing outbreaks.

Dr. K. Vijaya Director, Youth Health Division Singapore Health Promotion Board

The Singapore Health Promotion Board (HPB) advocates eight target areas for effec-tive hand washing (Box).

Diagnosing HFMDPrimary 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 Sin-gapore 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 ap-proximately 1 week and patients may only present with a sore mouth or throat. There-fore, symptoms may not be apparent initial-ly 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 but-tocks, arms and legs

• Mouth ulcers • Vomiting and diarrhea • Tiredness and weakness

A child is infectious throughout the dura-tion of the illness.

23 November 2012 In Pract iceLaboratory testing is available to isolate

and identify the causative agent. Howev-er, testing is usually not necessary because HFMD diagnosis is typically based on clinical grounds.

Treating HFMD There is no specific treatment for the infec-

tion 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 caregiv-ers 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 irritabil-

ity • Fits • Severe headache, dizziness or neck stiff-

ness • Breathlessness or turning blue • Dehydration – this can happen due to con-

tinuous 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 fol-

low up care. Physicians should closely moni-tor young children (especially infants) for development of dehydration. Rarely, patients with central nervous system manifestations of HFMD such as encephalitis or aseptic men-ingitis may require hospitalization.

HFMD is highly contagious. A child is also susceptible to getting other infections when they have HFMD. Physicians can advise par-ents 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 ad-ditional precautions to prevent the spread of HFMD.

• Keep the child at home until he or she is ful-ly 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, kinder-gartens and schools.

24 November 2012 Conference Coverage

EASD/ADA promote individualized therapeutic goals in T2DM

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

Leonard Yap

The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have re-

leased 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 previ-ous guidelines, the new statement advocates more patient involvement and gives guidance on the rational approach to the choice of ther-apy. 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 inter-ventions they use, said Boulton, adding that implementation of therapy occurs in the con-text 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

complications, but always keeping in mind the potential adversities with treatment bur-den, 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 recom-mendations regarding the intensiveness of glycemic therapy focused on a HbA1c target of below 7 percent. The statement empha-sized the need to be pragmatic and to keep goals individualized.

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

25 November 2012 Conference CoverageThe long-term effects of T2DM reveal

themselves over the course of decades, which makes distinguishing the effects of medical interventions difficult, said Dr. Silvio Inzuc-chi, 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-

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.”

The precise glycemic target takes into ac-count several factors including patient’s at-titude and expected treatment efforts, risks associated with hypoglycemia and other adverse effects, disease duration, life expec-tancy, other co-morbidities, established vas-cular 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 com-pared with a younger newly-diagnosed per-son that is otherwise healthy.

The position statement pointed out that there is a need for numerous studies in spe-cific subgroups of people of different ages and with different stages of diabetes, in order to assess the various possible combinations of glucose-lowering therapies.

Key points from the position statement: • Diet, exercise and education remain

the foundation of any type 2 diabetes treatment program

• Unless there are prevalent contraindi-cations, metformin is the optimal first-line drug

• After 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 combina-tion with other agents to maintain glu-cose control

• Comprehensive cardiovascular risk reduction must be a major focus of therapy

This approach is

particularly appropriate

in T2DM

‘‘


Enterovirus may be linked to type 1 diabetes


Leonard Yap

An enterovirus infection may be a cause of type 1 diabetes (T1D) in some patients, says an expert.

Evidence suggests that an infection of pan-creatic islet beta-cells with one or more sero-types of enterovirus may contribute to the de-velopment 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 epidemio-logical studies undertaken across popula-tions, to the isolation of productive virus strains from individual pancreas samples [in rare cases],” Morgan said. “However, despite the increasing weight of evidence, the hy-pothesis that an enteroviral infection might play a role in the etiology of T1D remains un-proven.”

Morgan’s research team studied a collec-tion of pancreas samples recovered post-mor-tem from patients who died soon after a diag-nosis of T1D. This cohort was used to study both viral protein expression and the estab-lishment of anti-viral response mechanisms at the level of individual islet cells. The team’s aim was to determine whether individual is-let endocrine cells displayed evidence of viral infection in human T1D and to establish, at the molecular level, how the cells responded to such infection.

By monitoring expression of the enterovi-ral capsid protein, VP1, as a marker of infec-tion, it was revealed that more than 60 per-cent of the pancreatic samples tested positive for enteroviral infection. However, within any given patient, only about 20 percent of insulin-containing islets expressed immuno-reactive VP1 and the overall proportion of available β-cells that expressed VP1 was small (about 5 percent). A similar prevalence of im-munopositivity 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, in-cluding protein kinase R (PKR) and myeloid cell leukemia-1 (Mcl-1), in concert with VP1.

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

27 November 2012 Conference CoveragePKR is an enzyme responsible for the activa-tion of antiviral cascades within cells and is known to be induced during enteroviral in-fection. It is activated by the presence of viral dsRNA and leads to the rapid arrest of global protein synthesis by virtue of increased phos-phorylation of the initiation factor eIF2α. Mcl-1 is an anti-apoptotic protein which is subject to rapid turnover in cells, such that it is de-graded quickly during the translational arrest that ensues following the activation of PKR.

“Collectively, our data imply that entero-viral infection can be detected within a small proportion of β-cells in the majority of pa-tients 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 hy-pothesis that the progression of human type 1 diabetes may be influenced by beta-cell en-teroviral infection.”

Morgan believes that it is entirely possible that additional mechanisms beyond enterovi-ral 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 un-der conditions when they produce minimal amounts of viral protein,” he added. “Hence, the failure to detect them by analysis of pro-tein production in tissue sections does not necessarily mean they are not there.”

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Stroke risk high in diabetes patients


Alexandra Kirsten

Type 2 diabetes is associated with an in-creased 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 cumula-tive stroke incidence of 12 percent over a 10-year 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 popula-tion,” 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, albu-minuria, and co-existing complications and co-morbid states, were recorded at baseline and every year during the 10-year study pe-riod. Morbidity and mortality due to stroke were determined and correlated with poten-tial 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 peri-od, 135 new episodes of stroke (in 7.5 percent

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 glyce-mia (95% Cl 1.17-3.39; P<0.05), daily albumin-uria (95% Cl 1.02-4.06; P<0.05), atrial fibrilla-tion (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.

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


Insulin infusions beneficial in diabetics post-stroke


Alexandra Kirsten

Patients with type 2 diabetes who experi-ence an acute episode of stroke seem to

benefit more from continuous intravenous in-sulin infusions than from intermittent subcu-taneous injections.

“Hyperglycemia is associated with [a] worse outcome in stroke patients,” said Leonid G. Professor Strongin from the State Medical Academy, Nizhny Novgorod, Rus-sia. “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 clin-ical study to compare the efficacy and safety of the two different insulin delivery meth-ods in patients with type 2 diabetes who had experienced a stroke. A total of 73 pa-tients were subdivided into two comparable groups within 24 hours of the stroke event, with one group assigned to receive continu-ous insulin infusions and the other intermit-tent 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 glu-cose 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 glu-cose levels faster (2-3h vs. 3-6h, P=0.0019) and showed a smaller amplitude of fluc-tuations of glycemia (0.95 mmol/L vs. 5.3 mmol/L, P<0.01). The frequency of hypogly-cemia was significantly lower in the infusion group than in the comparison group (9 per-cent 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 af-ter 6 months (62 vs. 47, P=0.006). However, there were no significant differences in hos-pital 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 intra-venous 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 adminis-tration on 6-month survival could not be proved.”


Exercise lowers CV risk in diabetics


Alexandra Kirsten

A 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 re-viewed data on leisure-time physical activ-ity 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 reg-ular exercisers were significantly less likely to have a cardiovascular event or to die ei-ther from cardiovascular disease or any other cause. The level of LTPA was related to fatal CV outcomes and all-cause mortality inde-pendently of conventional CV risk factors in type 2 diabetes. An increased LTPA level dur-ing the follow-up seemed to lower both CV risk and mortality in diabetic patients.

Those in the study who reported doing lit-tle 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 individu-als who did not improve their exercise hab-

its, the number of CV-related deaths among diabetics who increased their exercise levels fell by 67 per-cent (95% CI 0.17-0.60). Rates of all-cause mortality were reduced by al-most the same degree (95% CI 0.25-0.49).

“In general, diabetics are considered to

be less likely to engage in a regular exercise program than the general population,” stat-ed the researchers. However, approximately 1,800 patients moved from a low physical-ac-tivity 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 pharma-cological treatment are added,” Zethelius ex-plained. “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 dis-eases.”

It’s never too late to increase your physical

activity, a recent study suggests


Metformin can be used more widely, study suggests


Alexandra Kirsten

T he effectiveness and overall benefits of the antidiabetic drug metformin far outweighs its risks, even in patients

with renal impairment, according to a Swed-ish study.

“The long-term effectiveness and safety of glucose-lowering medications are under de-bate,” 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 pa-tients 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 cardiovascu-lar disease (CVD), acidosis/serious infection and all-cause mortality in all patients and in subgroups with different estimated glomeru-lar filtration rate (eGFR) intervals. The mean follow-up of the study was 3.9 years – equiva-lent 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 mortal-ity compared with metformin monotherapy (95 % CI 1.07-1.29 and 95% CI 1.19-1.50, re-spectively). In subgroup analyses, metformin was not associated with an increased risk of any of the outcomes in patients with eGFR 30-45, 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 mor-tality.

“In clinical practice, the benefits of metfor-min 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 guide-lines”, 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. Nev-ertheless, “it is important to keep in mind that the results are for patients with mild to mod-erate 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

Mandatory medical screening of older drivers – which has been im-posed in some European countries

and is proposed in the UK – is not evidence-based and may have dangerous consequenc-es, 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 train-ing 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-

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 cog-nitive 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 screen-ing among older patients in the clinical set-ting is of enormous value. Rather than mass screening, “we should focus on evidence based innovations, such as restricted licens-ing and rehabilitation, for people with age-related illness.”

Keep older drivers on the road, says expert

Alexandra Kirsten

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

33 Hepat i t isNovember 2012

Radha Chitale

Treating 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 In-stitute 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 pa-tients and adult patients, who were infected at birth or in the first year of life and had similar disease profiles, the researchers iso-lated T-cells from CHB patients of various ages and measured levels of inflammatory cytokines and the number of HBV-specific T-cells. [Gastroenterology 2012;143:637–645]

Their analysis showed that inflamma-tion 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 in-fection than adults with CHB.

International guidelines recommend de-laying treatment for CHB until the liver be-gins 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”,

in which the immune system does not rec-ognize or attack a disease target, until they grew older.

“Young patients have an immune re-sponse 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,” Ber-toletti said.

Typically, adults show signs of liver dam-age after the age of 30, by which time their T-cells 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 be-come adults,” Bertoletti said. “It could be that treating patients when they are younger could yield a better response.”

Children or young adults with CHB may benefit from earlier treatment

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

34 Hepat i t isNovember 2012

Prison inmates infected with hepatitis C virus (HCV) are just as likely to ben-efit from cornerstone antiviral treat-

ment with combination pegylated interferon (PEG-INF) and ribavirin as community pa-tients, a recent US study has shown.

In the study, rates of sustained viral re-sponse (SVR) did not differ between the two groups – 42.9 percent for incarcerated patients and 38 percent for non-incarcer-ated 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 au-thor 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 improve-ment to public health.”

Previous studies have shown that inmates were 156 times more likely to acquire hepa-titis 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 thera-py between incarcerated and non-incarcerat-ed 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 com-munity 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 treat-ment, is almost synonymous to a “cure.” Patients who achieve that status experience slower progression of liver disease, howev-er, a portion of patients relapse shortly after therapy is stopped.

“Our findings highlight the effectiveness of antiviral therapy in HCV-infected prison-ers and show that it is as successful as treat-ment for HCV patients in the general popu-lation,” 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.

Hep C therapy just as effective for prisoners

Elvira Manzano

35 Research ReviewsNovember 2012

C hemokine (C-C motif) receptor 5 (CCR5) promotes lymphocyte recruitment to

tissues involved in acute graft-versus-host disease (GVHD) after allogeneic hematopoi-etic stem-cell transplantation and, in animal experiments, giving anti-CCR5 antibody protects against GVHD.

Maraviroc is a non-competitive, slowly re-versible small-molecule antagonist of CCR5. Now US researchers have shown that mara-viroc may provide protection against GVHD. In vitro, maraviroc inhibited CCR5 internal-ization 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 transplanta-tion 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 in-cidence 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 graft-

versus-host disease. NEJM 2012;367:135–45.

Maraviroc to prevent visceral GVHD

ACE inhibitors, ARBs and pneumonia

It 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 editori-alist points to faults in the design of this study and disagrees with the suggestion given the uncertainty of present evidence.

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).


Reconstructive surgery for female genital mutilation

In the last 10 years female genital mutilation (FMG) has affected 130-140 million girls world-

wide, with 92 million in Africa. Now surgeons in France have reported the results of genital recon-structive 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 sur-gery were recovery of identity (99 percent), im-provement 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).


Racial differences in HIV infection in MSM

Black men who have sex with men

(MSM) make up about 1 percent of the US popu-lation, yet in 2009 nearly a quarter of all new HIV infections were in this group. A meta-analysis was conducted to ex-plain the extent and causes of this disparity.

The meta-analysis in-cluded 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).


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 seronega-

tive 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 per-son–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 sero-discordant 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).


Immunization against polio in Pakistan, Afghanistan

More 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 poliomy-

elitis 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, securi-ty 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 po-liomyelitis 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 feder-ally 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).


A study in Kenya, South Africa, and Tanzania has assessed the prophylac-

tic use of combined tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in women at increased risk of HIV-1 infec-tion, with negative results.

The trial included 2,120 sexually active HIV-negative women aged 18–35 years. Randomization was to TDF-FTC or place-bo once daily for 52 weeks and follow-up was every 4 weeks for 60 weeks. HIV infec-tion occurred in 33 women in the prophy-laxis 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-trans-ferase 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 ad-herence was low.

Prophylaxis with TDF-FTC was not ef-fective 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).

Antiretroviral prophylaxis for at-risk women


Telehealth: Is it worthwhile?

The British government spent £30 million over

3.5 years on an evaluation of telehealth care for people with diabetes, chronic ob-structive pulmonary disease (COPD) or heart failure. Government ministers have greeted the results with great enthusiasm but profes-sional responses have been more muted.Recruitment to the study took place in 179 general practices in England be-tween May 2008 and No-vember 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 abso-lute 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 signifi-cantly between the two groups.

There is a danger of too simplistic an interpretation of the results. It is not a matter of tele-health ‘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 November 2012 After Hours

S 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 interna-tional 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 in-serted into the walls, signs and fences to indi-cate 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 Malac-ca’s town square, the Stadthuys, easily distin-guishable by its red walls, sits beside Christ


Church, also built by the Dutch. In the town square, tourists mill around, snapping pic-tures 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 ves-sel 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 Por-tuguese, 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 histori-cal artifacts, guiding visitors through the his-tory of Malacca from its humble beginnings to its height of glory as a trading destination and onwards through the years of coloniza-tion 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 authen-tic Nyonya beaded slippers. While wander-ing about these streets, you may also be ‘ac-costed’ 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.


Crater cultureYen 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 tra-ditional 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 press-ing 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 lev-el, which gradually filled with water. Tens of thou-sands of years later, the Austronesian people trav-eled to Sumatra, made their way inland and found a beautiful lake ringed with forested dusky-blue sil-houettes 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 man-dolin, flute and drums is still used during ceremo-nies and festivities. At these events, ulos – cloth weaved with Batak designs – are folded length-wise and draped over a shoulder. Some Bataks on Samosir continue to live in houses called rumah adat, built with distinctive roofs that sweep up-wards on either end like buffalo horns, the gables adorned with elaborate carvings of thumb-print-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 pris-oners, or if a tribe member was accused of legal in-fringements 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 judi-cial council would have sat to decide the fate of a


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• Diveintothedeliciouscoolwatersof

the crater lake• Dancewiththelocalsinatraditional

Batak performance• Hikethepeaceful,rollinghillsof

Samosir and drink in the scenery• Takeasipofpalmfruittoddy

prisoner. If the prisoner was condemned to execu-tion, he would be beheaded; the body would be dis-posed 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 phys-ical well-being: a weakened tondi can lead to illness and even death. The blood and the liver, consid-ered 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 canni-balism. 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 spot-ted in the middle of rice paddies and agricultural fields along the dusty, empty roads of Samosir. Be-fore the advent of Christianity, however, the Batak religious worldview was animistic. Divina-tion and magic were commonly practised. Da-tuks – animistic shamans – recorded magic spells, healing charms, prophecies and other mystical notes in arcane Batak characters on push-tahas, books made of tree bark, folded and opened in concertina style.

Certain burial practices have endured until to-day. At death, the Bataks are buried twice. It was tra-ditionally believed that the tondi of a deceased per-son 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 typi-cally 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 nar-row 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 stat-ue of Anting Malela carved to adorn his tomb. Today, the sarcophagus is the object of tourist fascination and camera clicks.

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

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

48 November 2012 CalendarNovember 2012 Scientific Sessions of the American Heart Association 3/11/2012 to 7/11/2012 Location: Los Angeles, California, US Info: American Heart Association Tel: (1) 214 570 5935 Email: [email protected] Website: www.scientificsessions.org

8th International Symposium on Respiratory Diseases & ATS in China Forum 20129/11/2012 to 11/11/2012Location: Shanghai, ChinaInfo: UBM Medica Shanghai Ltd.Tel: (86) 21-6157 3888 Extn: 3861/62/64/65Fax: (86) 21-6157 3899Email: [email protected]: www.isrd.org

63rd Annual Meeting of the American Association for the Study of Liver Diseases9/11/2012 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 Congress25/11/2012 to 27/11/2012Location: Kyoto, JapanInfo: Japan Convention Services, Inc.Tel: (81) 6 6221 5931Fax: (81) 6 6221 5939E-mail: [email protected]: www2.convention.co.jp/idfwpr2012

December

National Diagnostic Imaging Symposium 2/12/2012 to 6/12/2012Location: Orlando, Florida, USInfo: World Class CME Tel: (980) 819 5095Email: [email protected]: www.cvent.com/events/national-diagnostic-imag-ing-symposium-2012/event-summary-d9ca77152935404eb-f0404a0898e13e9.aspx

Asian Pacific Digestive Week 20125/12/2012 to 8/12/2012Location: Bangkok, ThailandTel: (66) 2 748 7881 ext. 111Fax: (66) 2 748 7880E-mail: [email protected]: www.apdw2012.org

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

54th American Society of Hematology Annual Meeting8/12/2012 to 11/12/2012Location: Georgia, Atlanta, USInfo: American Society of HematologyTel: (1) 202 776 0544Fax: (1) 202 776 0545Website: www.hematology.org

17th Congress of the Asian Pacific Society of Respirology14/12/2012 to 16/12/2012Location: Hong KongInfo: UBM Medica Pacific LimitedTel: (852) 2155 8557Fax: (852) 2559 6910E-mail: [email protected]: www.apsr2012.org

49 November 2012 CalendarUpcoming

16th Bangkok International Symposium on HIV Medicine16/1/2013 to 18/1/2013Location: Bangkok, ThailandInfo: Ms. Jeerakan Janhom (Secretariat)Tel: (66) 2 652 3040 Ext. 102Fax: (66) 2 254 7574E-mail: [email protected]: www.hivnat.org/bangkoksymposium

28th Congress of the Asia-Pacific Academy of Ophthalmology17/1/2013 to 20/1/2013Location: Hyderabad, IndiaInfo: APAO SecretariatTel: (852) 3943 5827Fax: (852) 2715 9490 Email: [email protected]: www.apaoindia2013.org

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

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

23rd Conference of the Asia Pacific Association for the Study of the Liver7/3/2013 to 10/3/2013Location: SingaporeInfo: Gastroenterological Society of Singapore, The Asian Pacific Association for the Study of the LiverTel: (65) 6292 4710Fax: (65) 6292 4721Email: [email protected]: www.apaslconference.org

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

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

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