OSA can be successfully managed in primary care

July 2012

www.medicaltribune.com

OSA can be successfully managed in primary care

FORUM

IN PRACTICE Surviving the approaching tsunami of diabetes

CONFERENCE

Therapeutics in osteoporosis

AFTER HOURS Promising drug combination for breast cancer

Chengdu – Land of Tea, Tao and Pandas

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July 2012

OSA can be successfully managed in primary care Rajesh Kumar

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

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

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

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

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

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July 2012

Molecular switch boosts immune response Rajesh Kumar

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ingapore scientists have identified a molecular ‘switch’ that triggers the body’s innate immune response against viral infections. When turned on, the switch (called Bruton’s tyrosine kinase [BTK]) activates the production of interferons - a potent class of virus killers that enable the body to fight harmful pathogens such as dengue and influenza viruses. [PNAS 2012.DOI: 10.1073/ pnas.1119238109] This finding could pave the way for more effective therapies for humans that strengthen the body’s own immune response against viral infections, said the researchers from the Agency for Science, Technology and Research (A*STAR) Bioprocessing Technology Institute (BTI). They extracted a class of immune cells known as macrophages from both normal mice and from mice deficient in BTK and exposed them to dengue virus. The BTKdeficient immune cells were unable to produce interferons, and hence had much higher viral counts compared to the healthy immune cells that had high-levels of interferons to fight the virus effectively. To further demonstrate the critical role of BTK in anti-viral response, the team focused on BTK’s role in Toll-like Receptor 3 (TLR3) signaling. TLR3 is needed for cells to activate the interferon response when cells are infected by viruses. They examined the effect of having a perpetually “on” or “off” BTK switch in

Singapore scientists have identified a molecular switch which can activate antiviral interferon production.

TLR3 signaling and found that a perpetually active or “on” BTK switch enhanced the production of interferon, resulting in a stronger and more lasting anti-viral response with significant reduction in dengue viral counts. An always “off” BTK switch led to a poor anti-viral response with very low levels of interferons produced, and little protection against the infection.

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July 2012

Forum

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

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

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

East where persons with diabetes can buy only one vial of insulin. Each person gets their share of 20 units; just enough to keep them alive and functioning. When I hear that 380 million people in the world are expected to have diabetes by 2025, I don’t see a number. I see people like my patients and these villagers who struggle everyday to live a life with a disease that demands so much and gives back so little. We are currently in the midst of a ‘tsunami’ of diabetes. Its first wave is the ever rising wave of obesity, the underlying current of the increase in diabetes. Worldwide, 2.8 million people die as a result of being overweight or obese and the prevalence of obesity has doubled between 1980 and 2008. North America leads the trend with more than 30

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Forum

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

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

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Indonesia Focus

Local events calendar

Pertemuan Ilmiah Ilmu Penyakit Dalam 2012 – PIT IPD 2012 Facing The New Challenges of Infectious Diseases : The Art of Antimicrobial Jakarta, 12 – 15 Juli 2012 Hotel Grand Sahid, Jakarta Sekr : Departemen Ilmu Penyakit Dalam – FKUI/RSCM Jl. Diponegoro 71, Jakarta Telp : 021 – 314 2108, 3193 0956 : 021 – 314 2108, 3193 Fax 6736 Email : [email protected] Website : www.internafkui.or.id/ pit2012 54th Anniversary PAPDI JAYA Preset: Jakarta Internal Medicine in Daily Practice 31 Agustus-2 September 2012, Jakarta Hotel Borobudur, Jakarta Sekr : Gedung ICB Bumiputera Lt.1, Jl. Probolinggo 18, Gondangdia, Menteng, Jakarta 10350 Tel : 021-2301267 Fax : 021-2301267 Email : [email protected], [email protected] The 14th International Meeting on Respiratory Care Insonesia (Respina) 2012 Jakarta, 5-6 Oktober 2012 Hotel Shangri-la, Jakarta Sekr : Gedung Asma Lt.2, Jl. Persahabatan Raya No.1, Jakarta 13230 : 021-47864646, Tel 47864321 Fax : 021-47866543 Email : info.respina@yahoo. com, info.respina. [email protected] Website : www.respina.org

2012 ISICM End Year Symposium Makassar, 10 – 13 October 2012 Sekr : Indonesian Society of Intensive Care Medicine (Perhimpunan Dokter Intensive Care Indonesia; PERDICI) Gedung Makmal Lt. 2 Komplek FKUI, Jl. Salemba Raya No.6 : 021- Tel 68599155/31909033 Fax : 021-31909033 Email : [email protected] Website : www.perdici.org The 9th Congress of Asian Pasific Federation of Societies for Surgery of the Hand in conjunction with The 5th Congress of the Asian Pasific Federation of the Societies for Hand Therapist Bali, 11-13 Oktober 2012 Grand Hyatt Bali Sekr : Jl. Pucang Anom Timur III No.65, Surabaya, Jawa Timur, Indonesia Tel : 021-63869502 Fax : 021-63869503 Email : apfssh2012@pharma- pro.com Website : www.apfssh2012.org The 35th Annual Scientific Meeting of Indonesian Urological Association Jakarta, 12-14 Oktober 2012 Hotel Gran Melia, Jakarta Sekr : Departemen Urologi, RSCM, Jl. Diponegoro No.71, Jakarta 10430 Tel : 021-3152892, 3923631 Fax : 021-3145592 PIT IKA V Bandung, 13-17 Oktober 2012 Hotel The Trans Luxury, Bandung Sekr : Ikatan Dokter Anak Indonesia, Cabang Jawa Barat Departemen Ilmu Kesehatan Anak,

Fakultas Kedokteran Unpad RS Dr. Hasan Sadikin Jl. Pasteur No.38 Bandung – 40161 Tel : 022-2039512 Website : www.pitika5.com 10th Asia and Oceania Thyroid Association Congress Bali, 24-27 Oktober 2012 Discovery Kartika Plaza Hotel, Bali Sekr : Divisi Endokrin, Fakultas Kedokteran Universitas Padjajaran Jl. Pasteur 38, Bandung 40161 Tel /Fax : 022-2033274 Email : [email protected] Website : www.aota2012.com KOPAPDI XV Medan Medan, 12-15 Desember 2012 JW Marriot International, Aryaduta, Grand Aston, Medan Sekr : Departemen Penyakit Dalam Fakultas Kedokteran Universitas Sumatera Utara /RS Umum Pusat H. Adam Malik Lt. III , Jl. Bungalau 17, Medan Tel/Fax : 061-4528075 Email : papdicabsumut@gmail. com, kopapdixv@pharma- pro.com Website : www.kopapdimedanxv. com

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Indonesia Focus

Perlunya diagnosis dini pada GBS dan MG Hardini Arivianti

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angguan neuro-imunologi memiliki spektrum yang luas, dan selain mengenai susunan saraf pusat juga dapat mengenai susunan saraf tepi. Gangguan pada saraf perifer merupakan penyakit yang sering dijumpai dalam praktek sehari-hari di bidang neurologi. Ketua Perhimpunan Dokter Spesialis Saraf Indonesia (PERDOSSI) Cabang Jakarta, dr Darma Imran, SpS (K), menjelaskan kelumpuhan neurologis yang diakibatkan stroke, Guillain-Barre Syndrome (GBS) atau infeksi otak lainnya, menimbulkan gejala yang hampir sama. “Langkah pertama yang penting adalah menegakkan diagnosis terlebih dahulu yang nantinya sangat diperlukan untuk pengobatan sehingga kualitas hidup pasien dapat lebih baik.” Yang kedua, kasus kelumpuhan ini lebih kecil dibandingkan dengan kasus DBD dan diare. Namun, lanjut dr. Darma, kelumpuhan yang ditimbulkan ini menimbulkan beban tersendiri yang lebih besar, baik perawatan maupun terhadap keluarga, padahal beberapa masalah kelumpuhan dapat sembuh dengan baik, misalnya GBS tipe tertentu asalkan diagnosa dan terapinya tepat. Saat ini, diagnosis GBS mengalami perkembangan sangat pesat dan berdasarkan manifestasi klinis, analisa LCS, elektrofisiologi dan serologi. “Secara epidemiologis, GBS termasuk penyakit yang sangat jarang,” tukas dr. Manfaluthy Hakim, SpS(K). Angka kejadian 0,5-1,5/100000 penduduk dan angka ini sama baik di negara maju maupun berkembang. Gejala yang ditimbulkan adalah rasa kesemutan yang dimulai dari ujung kaki atau tangan,

simetris dan naik ke atas lalu berlanjut menjadi kelumpuhan. Penyakit ini merupakan ‘Acute Inflammatory Demyelination Polyneuropathy’ (AIDP) yang ditandai dengan kelemahan otot progresif dan arefleksia. “GBS merupakan penyebab utama kejadian paralisis akut setelah era polio dan perlu mendapat perhatian karena selama periode 2010-2011 ada 48 kasus GBS dari berbagai varian di RSCM”.” Dibandingkan dengan tahun sebelumnya, kasus ini meningkat. Kadangkala dari beberapa penelitian, kurang lebih 4-6 minggu sebelum rasa kesemutan muncul, pasien mengalami demam, kemungkinan disertai dengan

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Indonesia Focus

diare dan radang tenggorokan. Hal tersebut yang memicu antibodi. Pemeriksaan Pada pemeriksaan fisik GBS dapat ditemukan hilangnya refleks tendon. Perlu diketahui pula riwayat ada tidaknya infeksi sebelumnya dan pemeriksaan tambahan lainnya bisa dilakukan analisa cairan otak, yang keduanya dapat mendukung diagnosa kemungkinan adanya GBS. Pada GBS juga dapat dilakukan pemeriksaan kecepatan hantar saraf yang dapat mengetahui adanya GBS lebih dini dibandingkan dengan pemeriksaan analisa cairan otak Pemeriksaan ini juga bisa dilakukan untuk mendeteksi myasthenia gravis (MG). ”Menilai respon serabut otot juga bisa dilakukan pada MG,” tukas dr Manfaluthy. Pada salah satu sesi simposium ’Peripheral Nerve Disorder Focus on Guillain-Barre Syndrome and Myasthenia Gravis’ beberapa waktu lalu, dr. Manfaluthy juga memaparkan, pada analisa LCS ditemukan peningkatan protein tanpa disertai dengan peningkatan sel yang signifikan. ”Namun pada beberapa penelitian menemukan LCS hampir selalu normal pada minggu-minggu pertama dan baru meningkat (90%) pada akhir minggu pertama atau awal minggu kedua,” jelas Kepala Divisi Neurofisiologi Klinik dan Penyakit Neuromuskular, FKUI-RSCM ini. Kadar protein LCS ini tidak berkaitan dengan outcome pasien GBS. Pengobatan GBS Pemulihan, perbaikan dan outcome pasien GBS ditentukan oleh kecepatan dalam memberikan terapi, sehingga perlu menegakkan diagnosis sedini mungkin. Jenis terapi yang direkomendasikan saat ini adalah dengan

pemberian Intravenous Imunoglobulin (IVIG) dan plasmapheresis. Diagnosis dini GBS pada 2 minggu pertama dari mulainya gejala awal berupa kesemutan. Biasanya pasien saat kesemutan tidak ’aware’. Bila terapi diberikan pada 2 minggu pertama hasilnya jauh lebih baik. Bila terapi terlambat diberikan, angka kecacatan pun akan lebih tinggi. ”Pemulihan mulai terjadi pada 8-12 minggu dan pada pasien yang diberikan IVIG, hari ke 6-7 pasien sudah mulai merasakan perbaikan,” tukas dr. Manfaluthy. Sekitar 80-90% pasien GBS akan meninggalkan gejala sisa berbagai bentuk, dan yang tersering berupa rasa kelelahan, baal pada kaki dan tangan. Kekambuhan GBS dipengaruhi oleh varian atau bentuknya. Pada tipe ‘Acute Motor Sensory Axonal Neuropathy’ / AMSAN, perbaikannya lebih kecil dibandingkan tipe ‘Acute Motor Axonal Neuropathy ‘/AMAN. Prinsipnya, ‘Acute Inflammatory Demyelinating Polyradiculoneuropathy’/ AIDP tidak akan kambuh sedangkan ‘Chronic Inflammatory Demyelinating Polyneuropathy’ / CIDP bisa berulang lagi. GBS pada anak Selanjutnya dr. Dwiputro Widodo, SpA(K) menjelaskan penelitian restrospektif pada 4 rumah sakit di Jakarta. Populasi target adalah seluruh anak dengan GBS pada periode 20092011 yang menjalani pengobatan dengan IVIG dan plasmapheresis, dan ada 5 anak tanpa pengobatan. Diagnosis didasarkan pada gejala klinis, analisa LCS dan elektrofisiologi. Pengelolaan pasien ditujukan kepada tindakan suportif dan fisioterapi. Perbaikan klinis awal dapat terlihat pada hari ke-2 atau ke-3 setelah pemberian IVIG. Mengenai pengobatan, dr. Dwiputro menjelaskan, sesuai guideline EFNS (2008)

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Indonesia Focus

IVIG menjadi pilihan utama pada anak, karena lebih mudah penggunaannya dan efek samping lebih kurang dibandingkan dengan plasmapheresis. Meskipun mekanismenya belum diketahui dengan jelas, kemungkinan adanya inaktivasi antibodi mielin spesifik atau menghambat produksi antibodi, dan menghambat aktivasi komplemen sehingga menimbulkan perbaikan kecepatan hantar saraf. Selain itu, netralisasi sitokin dan solubilisasi kompleks imun juga bisa menjadi mekanisme pengobatan tersebut. Myasthenia gravis Myasthenia gravis (MG) merupakan gangguan autoimun yang merusak paut saraf otot sehingga menyebabkan gangguan transmisi saraf-otot dan gangguan kontraksi otot. Tiga jenis MG adalah bulbar, okular dan general (mengenai otot-otot sentral/pangkal) dan tipe yang paling sering terjadi adalah tipe okular. Manifestasi klinis tersering adalah okular ptosis dan diplopia. Prevalensi MG diperkirakan sekitar 0,514,2 kasus/100.000 orang. Sedangkan periode 2010-2011 di RSCM didapatkan 94 kasus, dan kasus ini 2 kali lebih banyak dibandingkan GBS. Ada beberapa kondisi MG tertentu yang perlu diwaspadai. Penyakit ini pada orang dengan aktivitas fisik tinggi dapat menimbulkan gejala berat yaitu krisis miastenia yang

kadangkala pasien mengalami kesulitan bernapas. Kemudian ada kondisi emergensi lainnya, yaitu krisis kolinergik akibat penggunaan obat yang berlebihan. Efek kolinergik ini menimbulkan pengeluaran cairan/ lendir secara berlebihan dari saluran napas atau tenggorokan sehingga dapat menyumbat jalan napas. Dokter perlu mengenal gejala klinis dengan baik. “Tes sederhana yang bisa dilakukan pada MG adalah dengan ice pack. Pada yang tipe okular, setelah mata dikompres selama 3 menit, maka penglihatannya kembali jelas,” tambah dr. Manfaluthy. Penyakit ini perlu mendapat perhatian serius karena sekitar 15-20% pasien memiliki risiko mengalami episode krisis miastenia yang mengancam jiwa dalam 2 tahun setelah terdiagnosis. Selain autoimun, MG dikaitkan dengan kelenjar timus yang seharusnya menghilang setelah masa kanak-kanak. Pada beberapa orang, kelenjar ini persisten atau tumbuh menjadi tumor (timoma). Menurut dr. Ahmad Yanuar, SpS pada salah satu sesi simposium, menjelaskan mengenai penatalaksanaan MG terdiri dari terapi inisial/simtomatik (AChE inhibitor: pyridostigmin bromide), terapi yang bertujuan menekan sistem imun (timektomi, kortikosteroid dosis tinggi, steroid sparing medication) dan terapi jangka pendek /emergensi (IVIG dan plasmapheresis).

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Pentingnya pemeriksaan spirometri Hardini Arivianti

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ada tanggal 27 Juni 2012 lalu telah ditetapkan sebagai ’Hari Spirometri Sedunia’ oleh ‘European Respiratory Society’ (ERS), ‘American Thoracic Society’ (ATS) dan ‘Asian Pacific Society of Respirology’ (APSR). Pemeriksaan spirometri ini sangat penting karena dengan alat sederhana ini dokter dapat mendeteksi atau mendiagnosis beberapa penyakit dengan cepat. Salah satu penyakit yang dapat terdeteksi adalah Penyakit Paru Obstruktif Kronik (PPOK) dan kematian akibat penyakit ini meningkat 2 kali lipat serta menjadi masalah besar di dunia,” jelas dr. Arifin Nawas, SpP(K) selaku Ketua Umum Perhimpunan Dokter Paru Indonesia (PDPI) tanggal 27 Juni lalu dalam rangka memperingati ‘Hari Spirometri Sedunia’. Spirometri dan penyakit paru Spirometri merupakan pemeriksaan baku emas pada PPOK dan merupakan alat pengukur ventilasi untuk mengukur volume statik dan volume dinamik paru. Volume statik meliputi volume tidal (VT), volume cadangan inspirasi (VCI), volume cadangan eskpirasi (VCE), volume residu (VR), kapasitas vital (KV), kapasital vital paksa (KVP), kapasitas residu fungsional (KRF), dan kapasitas paru total (KPT). Sedangkan volume dinamik mencakup volume ekspirasi paksa pertama (VEP1) dan maximal voluntary ventilation (MVV). Indikasi pemeriksaan spirometer ini adalah setiap keluhan sesak, pasien asma stabil, PPOK stabil, evaluasi pasien asma

setiap tahun dan PPOK setiap 6 bulan, persiapan operasi, pemeriksaan periodik pada pekerja yang terpapar partikel-partikel tertentu dan pemeriksaan periodik pada perokok. Hal ini diungkapkan oleh Prof. Dr. dr. Faisal Yunus, SpP (K). Tujuan dilakukan uji spirometri ini adalah untuk mengevaluasi status fungsi paru (normal, restriksi, obstruksi dan campuran), evaluasi terapi, memonitor riwayat penyakit, menilai prognosis dan menilai dampak pembedahan. Penyakit PPOK diproyeksikan menjadi penyebab kematian ketiga pada tahun 2020 nanti, setelah penyakit jantung iskemik dan penyakit kardiovaskular. Di Indonesia menurut SKRT (2005) asma, bronkitis kronik, dan emfisema menduduki peringkat ke-5 dari 10 penyebab kematian. Jumlah kasus PPOK juga meningkat karena peningkatan usia harapan hidup, prevalensi merokok yang makin tinggi dan tingkat polusi yang makin tinggi. ”Pada PPOK aliran udara terbatas karena elastisitas alveolus terganggu, struktur-struktur pendukung berkurang dan jalan udara menyempit,” lanjut Prof. Faisal. Pemeriksaan spirometri ini dilakukan dengan subyek dalam posisi berdiri, melakukan manuver setelah steady state dan pemeriksaan dilakukan sampai didapat 3 hasil yang dapat diterima dan dua diantaranya reproduksibel. Hasil yang dapat diterima, lanjut Prof Faisal, adalah permulaan uji harus baik, dan saat pemeriksaan selesai, pada hasil pemeriksaan akan

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tampak grafik flow-volume yang memiliki puncak. Yang dimaksud reproduksibilitas adalah setelah mendapat 3 manuver yang dapat diterima dari pemeriksaan dan bila nilai terbesar perbedaannya kurang dari 5% atau kurang dari 100 ml untuk nilai KVP dan VEP1. Pemeriksaan dikatakan tidak baik bila permulaan ekspirasi ragu-ragu/lambat, batuk saat ekspirasi, manuver valsava, ekspirasi yang tidak selesai, terdapat kebocoran, mouth piece tersumbat dan meniup lebih dari 1 kali.

Jumlah pemeriksaan maksimal adalah 8 kali, dan bila belum didapat hasil yang diharapkan, pemeriksaan diulang pada hari lain. Hasil spirometri dikatakan normal KVP dan KV > 80% nilai prediksi, VEP1 > 80% nilai prediksi dan VEP1/KVP > 75%. ”Pemeriksaan ini harus dilakukan dengan persiapan pasien (bebas rokok minimal 2 jam, tidak boleh makan terlalu kenyang, berpakaian tidak ketat), peralatan (kalibrasi minimal sekali seminggu), dan teknisi yang terlatih.”

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July 2012

Conference Coverage

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

Promising drug combination benefits HER2+ breast cancer patients Radha Chitale

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

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

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

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

Radiation therapy in childhood increases breast cancer risk Radha Chitale

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

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

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July 2012

Conference Coverage

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

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

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

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

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July 2012

Conference Coverage

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

Afatinib delays progression in advanced lung cancer Christina Lau

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

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

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

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

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July 2012

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

Regorafenib offers hope for GIST patients failing TKIs Christina Lau

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

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

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Conference Coverage

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

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

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July 2012

Conference Coverage

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

Better strategies needed for ALL in adolescents and young adults Christina Lau

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

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

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Conference Coverage

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

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

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July 2012

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

Feeding, not starving, tumors improves response to therapies and overall survival Radha Chitale

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ancer patients may live longer if their tumor microenvironment is normalized, rather than starved of blood and other nutrients, so that therapeutic treatments are more effective, said Professor Rakesh Jain, of the Steele Lab for Tumor Biology, Massachusetts General Hospital, Harvard Medical School in Boston, Massachusetts, US. This approach has implications for the half billion people worldwide with diseases characterized by abnormal vessels, he said. As tumors grow, vessels can become disorganized, misshapen or blocked, creating areas without oxygen. This hypoxic environment creates high interstitial fluid pressure and contributes to genetic instability, angiogenesis, resistance to cell death and metastasis. However, chemotherapy, radiation therapy and immunotherapy are demonstrably more effective when the tumor microenvironment is in a normal state. In a study of 30 patients with recurrent glioblastoma treated with an anti-vascular endothelial growth factor (VEGF), seven had increased tumor blood perfusion for more than 1 month, which was associated with increased survival of 6 months compared to patients in whose tumors blood perfusion remained stable or decreased (P=0.019). [Cancer Res 2012;72:402-407] “Normalization induced blood flow has the potential to increase survival in patients,”

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

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

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July 2012

Conference Coverage

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

Acute cancer drug shortages due to manufacturing, quality control Radha Chitale

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

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

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Conference Coverage

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

Bevacizumab slows down ovarian cancer progression Elvira Manzano

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

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

Sponsored symposium highlight

Rotavirus Gastroenteritis: Perspective and Prevention in Children Infeksi rotavirus umumnya ditemukan pada bayi berusia 6 bulan sampai 23 bulan, yang dapat memberikan dampak yang cukup besar dan meningkatkan mortalitas. Pencegahan infeksi rotavirus dengan vaksinasi, patogenitas bayi, efektivitas dan keamanan vaksin dibahas oleh Dr. Muzal Kadim, Sp.A(K) dan Prof. DR. Dr. Sri Rezeki S.Hadinegoro,Sp.A(K) serta moderator Dr. Sukman Tulus Putra, Sp.A(K) pada acara PKB ke-63 di Jakarta 17 Juni 2012 yang lalu.

Rotavirus Diarrhea in Children

The Challenge in Rotavirus Gastroenteritis Prevention in Children

Dr. Muzal Kadim, Sp.A(K) Departemen Ilmu Kesehatan Anak Divisi Gastrohepatologi Fakultas Kedokteran Universitas Indonesia RSCM Jakarta

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truktur rotavirus memiliki inti (core) yang dilapisi oleh kapsul dalam (inner capsid) dan kapsul luar (outer capsid). Kapsul luar terdiri dari glikoprotein VP7/protein G dan protease protein VP4/protein P yang berperan menentukan strain virus, sehingga digunakan untuk klasifikasi serotipe rotavirus (P dan G). Walau setiap negara memiliki strain yang berbeda dan bervariasi dari tahun ke tahun, tercatat lebih dari 95% infeksi rotavirus di dunia disebabkan oleh 5 serotipe G (G1, G2, G3, G4, dan G9). Berbeda dengan bakteri, penyebab diare yang lain, rotavirus menyebabkan atrofi jonjot mukosa usus halus dan absorpsi saluran cerna akan terganggu, sehingga terjadi fluktuasi air dan elektrolit yang menyebabkan diare. Selain itu enterotoksin rotavirus meningkatkan gerakan usus, sehingga volume cairan dalam lumen meningkat dan juga menyebabkan diare. Infeksi rotavirus dapat disertai demam dan muntah.Walau kerusakannya reversibel, namun diare akan berlanjut hingga vili saluran cerna beregenerasi. Penelitian multisenter rotavirus di Indonesia, mendapatkan data infeksi rotavirus

tertinggi di RSCM – Jakarta (67%), dan serotipe predominan yang didapatkan adalah G1,G2 dan G9. Karakteristik diare rotavirus dan non-rotavirus pada subyek studi tidak terlalu berbeda, kecuali pada gejala muntah yang ditemukan lebih menonjol pada infeksi rotavirus. Data Riskesdas 2007 menunjukkan kematian karena diare pada bayi dan anak usia 29 hari – 11 bulan dan 1 – 4 tahun di Indonesia menduduki urutan tertinggi, dengan persentase lebih dari 15%. Pencegahan diare rotavirus dengan pemberian ASI, cuci tangan, air bersih, dan sanitasi yang baik tidak memberikan hasil yang optimal dalam mencegah rotavirus, sehingga tetap diperlukan vaksinasi. Selain WHO, ESPGHAN dan ESPID pun merekomendasikan pemberian vaksin rotavirus secara masal di daerah dengan angka kematian karena diare >10% pada anak berusia <5 tahun. Jika pada data Riskesdas 2007 didapatkan kematian karena diare >15%, seharusnya pemberian vaksin rotavirus sebagai pencegahan diare seyogyanya diberikan sebagai perlindungan.

Tabel 1. Pasien dengan diare dan hasil tes rotavirus pada anak usia < 5 tahun di 6 rumah sakit di Indonesia (2006). Lokasi pasien

Rumah Sakit

Jumlah pasien

Jlm (%) pasien yang menjalani tes untuk rotavirus

Pasien diare dengan rotavirus (+) Jumlah

Presentasi pasien yang menjalani tes (95% CI)

Pasien rawat inap Palembang

Muhammad Husein

534

513 (96)

326

64 (60-68)

Jakarta

Cipto Mangunkusumo

106

99 (93)

66

67 (58-76)

Bandung

Hasan Sadikin

138

137 (99)

70

51 (43-59)

Yogyakarta

Sardjito

262

246 (94)

95

39 (33-45)

Denpasar

Sanglah

557

557 (100)

339

61 (57-65)

Mataram

Mataram

710

688 (97)

449

65 (61-69)

Subtotal

............

2307

2240 (97)

1345

60 (58-62)

Prof. DR. Dr. Sri Rezeki S.Hadinegoro,Sp.A(K) Departemen Ilmu Kesehatan Anak Divisi Infeksi dan Pediatri Tropik Fakultas Kedokteran Universitas Indonesia RSCM Jakarta

I

nfeksi rotavirus (RV) yang ditemukan sejak bayi lahir didapat dari lingkungan/masyarakat (community acquired) atau disebabkan oleh infeksi nosokomial atau hospital acquired. Studi Gleizes dkk mencatat bayi-bayi usia < 6 bulan dua kali lebih banyak terinfeksi RV di RS dibandingkan dari lingkungannya. Infeksi RV yang didapat pertama kali akan menyebabkan gejala yang sedang sampai berat, terlebih daya imun bayi belum sempurna, sehingga dapat menyebabkan dehidrasi berat dan kematian. Infeksi RV ke dua kalinya pada umumnya ringan, sedangkan infeksi RV ke-3, ke-4 dan ke-5 dapat asimtomatik (Gambar 1). Jadi, tujuan pemberian vaksinasi RV adalah meniru pembentukan daya proteksi akibat infeksi alamiah tanpa manifestasi klinis sehingga dapat melindungi dari infeksi pertama RV yang cenderung sedang sampai berat. Insiden RV tidak dapat dikontrol hanya dengan meningkatkan penyediaan air bersih dan menjaga sanitasi serta hygiene practices. Di Indonesia, Ikatan Dokter Anak Indonesia (IDAI) 2011 menganjurkan pemberian vaksin RV mulai usia 2 sampai dengan 6 bulan. Vaksin rotavirus ada 2 jenis yaitu animalbased vaccines (attenuated monovalent animal RV dan animal–human reassortant RV) dan human-based vaccines (attenuated monovalent human RV: 89 -12 strain: RIX 4414/ Human Rotavirus Vaccine (HRV) dan neonatal strain dari Australia). Bila berdasarkan strain, vaksin RV dibedakan atas one-strain vaccines dan multiple-strains vaccines. Pemberian vaksin HRV oral dibagi dalam 2 dosis dan interval pemberiannya harus diperhatikan. Vaksin HRV dapat mulai diberikan

sejak usia 6 minggu, dan dosis kedua harus lengkap pada usia 24 minggu, atau lebih baik apabila sebelum 16 minggu vaksin HRV telah lengkap diberikan. Beberapa penelitan dari strain monovalen G1 (HRV) yang di follow up selama dua tahun menemukan bahwa terdapat efikasi terhadap G1 dan juga menunjukkan efikasi terhadap serotipe lainnya, seperti G2, G3, G4 dan G9. Pemberian HRV bersama vaksin oral polio (OPV) tidak menyebabkan penurunan efikasi HRV terhadap kasus gastroenteritis berat. Vaksin HRV dapat diberikan bersama dengan vaksin lainnya. Dulu, pemberian vaksin RV yaitu Rhesushuman reassortant rotavirus vaccine (rotashield) menyebabkan bayi mengalami intususepsi pada minggu pertama setelah pemberian dosis pertama, sehingga vaksin ini ditarik dari peredaran. Pada perkembangan selanjutnya, dibuat vaksin yang lebih baru dan dilakukan penelitian klinis fase III skala besar, yaitu vaksin HRV (Human Rotavirus Vaccine) dengan total N=63.225. Hasil studi fase III mencatat pemberian vaksin oral HRV sebelum 31 hari memiliki risiko relatif (RR)= 0.85 (95%CI = 0.3;2.4) terhadap intususepsi. Studi pivotal lainnya dari HRV (Rota-023), juga mencatat efikasi dan keamanan vaksin HRV yang baik, dan tidak mendapatkan kenaikan risiko intususepsi pada pemberian HRV pada hari ≤31 setelah pemberian dosis HRV pertama dan pada 30-90 hari setelah dosis kedua. Keamanan vaksin rotavirus terhadap intususepsi juga telah diakui oleh WHO dan SAGE (Strategic Advisory Group of Experts).

Gambar1. Probabilitas infeksi rotavirus terhadap usia dan derajat keparahan infeksi

Tabel 1. Proteksi HRV terhadap berbagai tipe RV

Pasien rawat jalan Bandung

Hasan Sadikin

27

27 (100)

11

41 (22-58)

Yogyakarta

Sardjito

38

29 (76)

3

10 (1-21)

Mataram

Mataram

123

120 (98)

59

49 (41-59)

Subtotal

............

188

176 (94)

73

41 (34-48)

Sumber: Dikutip dari Soenarto et al. JID 2009:200 (Suppl 1).

Kesimpulan:

• • •

Insiden rotavirus di Jakarta mencapai 67%, dengan genotip predominan G1, G2, G9. Karakteristik muntah lebih sering dialami oleh anak-anak yang menderita diare karena infeksi rotavirus. Pencegahan diare rotavirus dengan ASI, cuci tangan, air bersih, dan sanitasi yang baik saja tidak cukup dalam mencegah rotavirus, sehingga tetap diperlukan vaksinasi. Sumber: 1.Ruiz-Palacios GM et al. New Engl J Med 2006; 354: 11–22. 2.Vesikari T et al. Lancet 2007; 370: 1757–63. 3. Linhares AC et al. Lancet 2008; 371: 1181–9. 4. Phua K et al. Vaccine 2009; 27: 5936–4.

The opinions expressed in this publication are not necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage howsoever arising is hereby disclaimed. © 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced by any process in any language without the written permission of the publisher. UBM Medica, 3rd floor, Aquarius Building, Jl. Sultan Iskandar Muda No. 7, Arteri Pondok Indah, Kebayoran Lama, Jakarta Selatan. Telp: 021-7292662, Fax: 021-7293539 Email: [email protected] Website: www.ubmmedica.com

• •

RV merupakan beban penyakit di negara industri dan negara berkembang (>500.000 kematian/tahun) Vaksin human rotavirus (HRV) menunjukan efikasi terhadap strain-strain seperti G1, G2, G3, G4, G9 HRV telah menunjukkan efikasinya dalam melawan RV gastroenteritis di berbagai negara dan berpotensi baik sebagai pencegahan dan memiliki keamanan yang baik.

ID/ROT/0006/12

Kesimpulan:

•

SAVE THE DATE

SINGAPORE 17 – 19 SEPTEMBER 2012 WWW.HIMSSASIAPAC.ORG/12

LINKING PEOPLE, POTENTIAL AND PROGRESS On the week of the Singapore F1 we are holding HIMSS AsiaPac12. It is the one healthcare IT event dedicated to connecting people and information in new ways to increase patient care and safety, reduce healthcare costs and improve quality of life across the entire continuum of healthcare.

FOUR HEALTHCARE INFORMATION TECHNOLOGY CONFERENCES IN ONE HIMSS AsiaPac12 debuts a new annual conference format that is unlike anything you’ve ever experienced. You will have access four conferences all under one roof. 1. HIT X.0 2. mHIMSS (Mobile Health) 3. Care in the Community 4. Standards and Interoperability

The exhibition will showcase over a hundred products and services. Experience live demonstrations and technology updates as well as new products and services. And don’t miss the IHE Interoperability Showcase!

Conference & Exhibition 17–19 SEPTEMBER 2012 MARINA BAY SANDS S I N G A P O R E

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transforming healthcare through IT ™

28

July 2012

News

New ESC guidelines for heart failure Rajesh Kumar

N

ew European Society of Cardiology (ESC) guidelines for heart failure (HF) diagnosis and treatment recommend that all patients with an ejection fraction of 40 percent or less receive a beta-blocker in addition to an ACE inhibitor (or an angiotensin receptor blocker [ARB] if an ACE inhibitor is not tolerated). In addition to the treatment for HF with reduced ejection fraction (HF-REF), the 2012 guidelines also include new algorithms for diagnosis of the patient with suspected HF and the management of acute HF. The new therapeutic recommendations, revised from the 2008 document, more specifically relate the treatment to effects with a focus on important clinical outcomes. [Eur Heart J 2012; DOI:10.1093/eurheartj/ehs104] Dr. John McMurray of the University of Glasgow, Scotland and chairperson of the new guidelines, said the diagnosis section recognizes the increasingly important role of cardiac MRI in evaluation of patients with HF and includes mid-regional proANP (pro-atrial natriuretic peptide) as a “rule-out” blood test in patients with suspected acute HF. The pharmacological therapy part has a new indication for the mineralocorticoid antagonist (MRA) eplerenone in patients with HF-REF and mild symptoms. This broadens the indication for an MRA to essentially all HF-REF patients remaining symptomatic despite adequate treatment with a beta-blocker and ACE inhibitor/ARB. “The addition of ivabradine to an ACE inhibitor, beta-blocker and MRA is also

recommended in HF-REF patients in sinus rhythm with a persistently high heart rate despite optimized beta-blocker dosing,” said McMurray. In the non-surgical devices section, the wider use of cardiac resynchronization therapy (CRT) in HF-REF patients with milder symptoms and in sinus rhythm is recommended. The new guidelines, however, acknowledge the uncertain role of CRT in patients in atrial fibrillation and in patients with non-left bundle branch QRS morphology. Transcatheter aortic valve replacement is recommended as a completely new treatment option in patients with severe aortic stenosis unsuitable for conventional surgical valve replacement, said McMurray. Key new developments in surgery are new evidence on the role of coronary revascularization from the STICH* trial and the growing evidence that ventricular assist devices (VADs) have an important role in the management of patients with end-stage heart failure. “The guidelines address the use of VADs both as a bridge to transplantation and, in highly selected patients, as ‘destination therapy’,” he said. The new guidelines also recognize that the presence of HF and left ventricular systolic dysfunction may alter therapeutic options for co-morbidities and that co-morbidities may also influence the use of HF therapies. “No substantive new evidence has emerged in the area of acute heart failure and this section of the guidelines has been shortened and extensively revised with some

29

July 2012

News

regarding of recommendations in keeping with the guidelines focus of improved clinical outcomes,” said McMurray. Non-pharmacological/device/surgical treatments other than exercise and multi-disciplinary intervention are not given a recom-

mendation or evidence grading in the new guidelines due to uncertainty about the value of some (eg, sodium restriction) and the lack of robust outcome data for others. *STICH: Surgical Treatment for Ischemic Heart Failure

30

July 2012

News

Blood donation can reduce cardiovascular risk Rajesh Kumar

B

lood donation can help overweight people with metabolic syndrome reduce their risk of cardiovascular disease, according to a small German study. In the study, just two sessions of bloodletting, 4 weeks apart, were enough to improve subjects’ blood pressure and markers of cardiovascular disease such as heart rate, blood glucose and HDL/LDL ratio, the researchers said. Accumulation of iron in the body is associated with hypertension and diabetes and bloodletting seems to reduce the iron load, thereby reducing the risk. To confirm this, researchers from University DuisburgEssen in Berlin randomized 64 patients with metabolic syndrome to iron reduction by phlebotomy (N=33) or a control group (N=31). The iron-reduction patients had 300ml of blood removed at the start of the trial and between 250 and 500ml removed 4 weeks later. Six weeks later, allowing plenty of time for blood volume to be replaced, the patients who gave blood had a significant reduction in systolic blood pressure compared with controls (from 148.5 mmHg to 130.5 mmHg in the phlebotomy group versus 144.7 mmHg to 143.8 mmHg in controls [95% CI -20.7 to -12.5; P=0.001]). The phlebotomy group also experienced significant reduction in blood glucose levels and heart rate, and an improvement in their LDL/HDL ratio. “Consecutive reduction in iron stores

was able to improve markers of cardiovascular risk and glycemic control,” said lead researcher Professor Andreas Michalsen from the Charité-University Medical Centre, Berlin, Germany. “Consequently blood donation may prevent not just diabetes but also cardiovascular disease for the obese. Obviously this treatment will not be suitable for people with anemia. However for those eligible for treatment, blood donation may prevent escalation of their condition.” There was no change in the BMI or waist circumference, but the researchers could not be sure if the participants had made any lifestyle changes that might have also contributed to the improvement in their cardiovascular disease markers. Larger trials with much longer observation period are, therefore, required to further evaluate the long-term effects and potential rebound effects of phlebotomy therapy, the researchers said. “[Meanwhile], adequately controlled phlebotomy could be considered as a cost-effective additional treatment option in metabolic syndrome…a beneficial health-related effect for blood donation might be a motivating factor to encourage more people to donate more blood, providing public healthcare benefits as well,” the researchers said. While the idea is appealing, Singapore’s Health Sciences Authority, which manages the country’s blood services, is not convinced yet. A spokesperson said global scientific

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July 2012

News

evidence on the issue is still insufficient, due to which people with chronic diseases will continue to be advised against blood donations for their own safety.

Critics said while iron load in blood is indeed detrimental to cardiovascular health, there were better ways to reduce the risk than bloodletting.

32

July 2012

News

Low-fiber diet linked to more visceral fat in teenagers Alexandra Kirsten

A

dolescents who eat less fiber tend to have more visceral fat and higher levels of inflammatory biomarkers. This was the main finding of a recent US study. [J Clin Endocrinol Metab 2012 May 16. Epub ahead of print. DOI:10.1210/jc.20121784] Dr. Samip Parikh and colleagues from the Georgia Health Sciences University in Augusta, Georgia, US, investigated associations of dietary fiber intake with inflammatory-related biomarkers and total and central adiposity. The 559 participants were American students, aged 14 to 18, recruited from local high schools in the city area of Augusta. It is estimated that American adolescents consume less than one-half of the recommended intake of dietary fiber (14g/1,000 kcal). The researchers measured inflammatoryrelated biomarkers in fasting blood samples of the participants. Up to seven 24-hour recalls were used to evaluate their diet. X-ray absorptiometry and magnetic resonance imaging were employed to measure visceral adipose tissue and fat-free soft tissue of the teens. After adjusting for age, race, physical activity and fat-free soft tissue mass, they observed that higher fiber intake was associated with lower visceral fat mass found

in and around organs in the abdominal cavity (P<0.05). A higher total fat mass was only found in boys (P<0.03). Teens consuming a low-fiber diet tended to have higher levels of the so-called acutephase proteins plasma C-reactive protein and plasma fibrinogen. Generally plasma concentrations of these proteins increase in response to inflammation in the body. Low-fiber consumers also showed lower levels of adiponectin, a protective protein exclusively secreted from fat cells which helps the body to use glucose, break down fatty acid and fight inflammation. “A recent development in obesity research is the concept that increased adiposity is characterized by greater systemic inflammation,” the authors explained. Different studies in the past showed that adipocytes and macrophages within the fat mass can secrete cytokines and acute-phase proteins. Consequently more visceral fat leads to a greater production of inflammatory-related factors. This chronic low-grade systemic inflammation is “a well-known risk factor for cardiovascular disease and diabetes,” they added. The researchers concluded that, while the mechanism remains unclear, “dietary fiber intake may play a protective role against disorders associated with obesity-related inflammation.”

33

July 2012

News

Drinking alcohol may trigger AF Alexandra Kirsten

A

lcohol consumption may be an important trigger for paroxysmal atrial fibrillation (AF), the results of a recent study suggest. Patients suffering from recurrent episodes of AF experience palpitations, fainting, chest pain, and have a higher risk of stroke and congestive heart failure. Alcohol has been recognized as a possible clinical trigger for AF since the 1970s, said senior study author Dr. Gregory Marcus, assistant professor of medicine in the division of cardiology, UCSF, San Francisco, California, US. ”But it remains unknown if these associations occur more often than would be expected by chance alone because of the lack of a comparator group in previous studies,” he added. Marcus and colleagues interviewed 223 patients with documented cardiac arrhythmia associated with alcohol consumption, of whom 133 had PAF and 90 had other supraventricular tachycardias (SVTs). [Am J Cardiol 2012; Epub ahead of print. DOI:10.1016/j.amjcard.2012.03.033] After adjusting for multiple confounding variables, the researchers found that patients with paroxysmal AF were 4.42 times more likely to report alcohol as an arrhythmia trigger compared with patients with SVTs (P=0.014). Additionally, patients with paroxysmal AF had a 2.02 greater chance of reporting vagal activity as an arrhythmia trigger than those with SVTs (P=0.044). Patients with a history of paroxysmal AF triggered by alcohol consumption were also more likely

A recent study suggests that cardiologists should advise their patients not to drink if they have episodes of palpitations in particular.

to have episodes provoked by vagal activity (P=0.045). Vagal triggers can include sleep, as well as digestive precipitants such as spicy foods, cold bolus of food or liquid and large meals with resultant gastric distension. “Alcohol consumption and vagal activity elicit PAF significantly more often than SVT”, concluded the authors. Alcohol and vagal triggers often were found in the same patients with paroxysmal AF, raising the possibility that alcohol may precipitate AF by vagal mechanisms. “It is important that we do not recommend alcohol because it is heart healthy,” Marcus explained. “However it is probably too strong and too early to recommend against alcohol.” Nevertheless, cardiologists should advise patients not to drink if they have episodes of palpitations, especially after drinking alcohol, or if they suffer from high blood pressure and heart failure.

34

July 2012

News

Tenofovir a reasonable choice in HIV-positive pregnancies Yen Yen Yip

A

nti-HIV drug tenofovir (Viread®, Gilead Sciences), recommended by the World Health Organisation as first-line anti-retroviral therapy (ART), has been found to be safe for use in pregnant women with HIV. The Development of Anti-Retroviral Therapy in Africa (DART) trial compared monitoring methodologies for ART, and collected information on the pregnancies, births and infants of HIV-positive women taking tenofovir-containing regimens in Uganda and Zimbabwe. The children were followed for a period of up to 4 years. “We observed no evidence that tenofovir versus non-tenofovir ART had any adverse effects on pregnancy outcomes or on congenital, renal, bone or growth abnormalities up to age 4 years among children born to women with severe HIV immunodeficiency at ART initiation and exposed throughout the intrauterine period,” the investigators reported. [PLoS Med 2012;9. Epub ahead of print] Prior to the trial results, concerns on the safety of tenofovir arose from animal studies, where tenofovir use in pregnant Rhesus macaques was associated with bone demineralization, impaired growth, and renal abnormalities in their offspring. The findings from DART did not support such concerns. The 1-year infant mortality rate among the 226 live births recorded in the study group (5 percent) was similar to the rates observed in the general population of the African region (2 to 4 percent), said the

investigators, and much lower than among babies born to untreated HIV-positive women. The babies in DART did not experience any bone fractures or kidney problems associated with tenofovir during the 4-year followup period. There was no effect on growth at 2 years of age. Rates of congenital abnormalities were also similar between tenofovir and non-tenofovir-exposed infants. None of the infants who were tested for HIV were positive, although testing was not 100 percent, the researchers reported. These findings are significant as the chances of HIV-positive women taking tenofovir while conceiving or going through pregnancy is likely to increase. “New recommendations to start ART earlier and evidence of reduced onward HIV transmission with earlier ART initiation” are some reasons behind this trend, according to the researchers. Furthermore, a recent study has shown that tenofovir-containing regimens can prevent HIV acquisition in HIV-uninfected women having sex with men. The study was limited by its relatively small sample size, the investigators acknowledged. “Detailed safety of tenofovir for preexposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.” However, given the scarcity of available data in such resource-limited settings in Africa, “tenofovir-containing ART is a reasonable choice in pregnancy and … tenofovir pre-exposure prophylaxis is also reasonable for women who are at high risk of seroconverting during pregnancy,” they stated.

35

July 2012

News

IUDs, implants significantly more reliable for contraception Radha Chitale

U

nplanned pregnancy is 20 times more likely for women on the pill or other forms of short term birth control than if she were using an intrauterine device (IUD) or contraceptive implant, report researchers from Washington University in St. Louis in Missouri, US. Oral contraceptive pills are the most common form of birth control by far among women in the US, the researchers reported, but their efficacy hinges on proper use. The same is true for vaginal rings and trans-dermal contraceptive patches. Annual failure rates of oral contraceptives are 9 percent in the general US population and 13 percent among teenagers. IUDs and sub-dermal implants have failure rates less than 1 percent. About half of the 3 million pregnancies that occur in the US each year are a result of contraceptive failure, the researchers said. “If there were a drug for cancer, heart disease or diabetes that was 20 times more effective, we would recommend it first,” said study author Dr. Jeffrey Peipert, of the Washington University School of Medicine, St. Louis, Missouri, US. “Unintended pregnancies can have negative effects on women’s health and education and the health of newborns.” The trial included 7,486 participants between ages 14-45 who were not using contraception or looking to switch contraceptive methods, who did not plan to become

pregnant in the coming 12 months, and who were sexually active or were planning to be within 6 months. [N Engl J Med 2012;366:19982007] Patients were counselled on the types and efficacy of short and long term birth control methods and their choice was provided free of charge. During the trial, 334 women became pregnant and the researchers determined that 156 of these were due to contraceptive failure. Twenty-one of the pregnant women had been using an IUD or an implant while 133 were on the pill, patch or ring. Pregnancy was also twice as likely among women under age 21 who used short-term contraception compared with older women using similar forms of birth control. The failure rate for women using the pill, patch or ring was 4.55 per 100 participant years and 0.27 for women using IUDs and implants. Over 80 percent of women using longterm contraception demonstrated continued use at 12 months compared with 49 to 57 percent among women on short-term contraception. The data matches previous work on unplanned pregnancy rates but the researchers emphasized the magnitude of discrepancy between short and long term contraception. They also reported unexpected demographic data in preferred contraceptive choice.

36

July 2012

News

Short-term contraception was more prevalent among younger, educated women with private insurance who had no children. Long-term contraception was favored by older, less educated women on public health insurance who already had children, characteristics that the researchers said are typically associated with higher rates of unplanned pregnancy.

“If more women used the highly effective, long acting reversible methods, we would expect a decrease in the number of unintended pregnancies, because there would be more women continuing to use contraception,” the researchers said, adding that lowering the cost of IUDs and implants might make it a more viable option for more women.

37

July 2012

In Practice

Therapeutics in osteoporosis: What every GP should know Associate Professor Leong Keng Hong Consultant Rheumatologist, Gleneagles Medical Centre, Singapore Adjunct Associate Professor, Yong Loo Lin School of Medicine, National University of Singapore

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

wrist. Of these, hip fracture is the most severe as it is associated with poor or slow healing after a surgical repair. Pathogenesis of osteoporosis Inadequate peak bone mass and imbalances in bone resorption and bone formation lead to structural deterioration and eventually, osteoporosis. Lack of estrogen as a consequence of menopause increases bone resorption and decreases bone deposition. Calcium metabolism may play an important role in bone turnover, as well as deficiency in calcium and vitamin D. Diagnosing osteoporosis As in any asymptomatic disease, a high index of suspicion is needed to diagnose osteoporosis. Fracture history at any site, fall history, height reduction and reduced body mass index (BMI) are important indicators, but the most significant clinical risk factors for validating osteoporotic fractures are age and weight, which have become the basis of the Osteoporosis Self-assessment Tool for Asians (OSTA) test. The OSTA test determines a patient’s risk of developing osteoporosis (high, moderate or low) and helps a physician decide who to send for a bone mineral density (BMD) test. A score of >20 in the OSTA test means the patient is at high risk, 0-20 equals moderate risk and <0 means low risk. Patients at high risk, or at moderate risk with other risk factors, should take a BMD test using a dual-energy x-ray absorptiometry (DEXA) scan. DEXA gives both the T score (deviation from the mean of the peak bone

38

July 2012

In Practice

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

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

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

39

July 2012

In Practice

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

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

40

July 2012

Calendar

July 38th Annual Meeting of Society of Pediatric Dermatology 11/7/2012 to 14/7/2012 Location: California, US Info: Society for Pediatric Dermatology Tel: (317) 202-0224 Fax: (317) 205-9481 Email: [email protected] Website: www.pedsderm.net

30th International Congress of Psychology 22/7/2012 to 27/7/2012 Location: Cape Town, South Africa Tel: (27) 11 486 3322 Fax : (27) 11 486 3266 E-Mail: [email protected] Website: www.icp2012.com

Healthcare in China 2012 24/7/2012 Location: Beijing, China Info: Economist Conferences Tel: (852) 2585 3312 Email: [email protected] Website: http://www.economistconferences.asia/event/HCCN

17th World Congress on Heart Disease 2012 27/7/2012 to 30/7/2012 Location: Toronto, Ontario, Canada Info: International Academy of Cardiology Tel: (1) 310 657 8777 Fax: (1) 310 659 4781 E-Mail: [email protected] Website: www.cardiologyonline.com

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

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

Upcoming European Respiratory Society Annual Congress 1/9/2012 to 5/9/2012 Location: Vienna, Austria Info: European Respiratory Society Tel: (41) 21 213 01 01 Fax: (41) 21 213 01 00 E-Mail: [email protected] Website: www.erscongress2012.org/

14th Congress of the International Society for Peritoneal Dialysis 9/9/2012 to 12/9/2012 Location: Kuala Lumpur, Malaysia Info: International Society for Peritoneal Dialysis Tel: (603) 2162 0566 Fax : (603) 2161 6560 E-Mail: [email protected] Website: www.ispd2012.org.my

Hospital Management Asia 2012 13/9/2012 to 14/9/2012 Location: Hanoi, Vietnam Info: Ms. Sheila Pepito Tel: (632) 846 8339 Email: [email protected] Website: hospitalmanagementasia.com

15th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2012) 3/10/2012 to 6/10/2012 Location: Florence, Italy Tel: (41) 22 908 0488 Fax: (41) 22 732 2850 Email: [email protected] Website: www.kenes.com/esid

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July 2012

Calendar

42nd Annual Meeting of the International Continence Society 15/10/2012 to 19/10/2012 Location: Beijing, China Tel: (41) 22 908 0488 Fax: (41) 22 906 9140 Email: [email protected] Website: www.kenes.com/ics

National Diagnostic Imaging Symposium 2/12/2012 to 6/12/2012 Location: Orlando, Florida, US Info: World Class CME Tel: (980) 819 5095 Email: [email protected] Website: www.cvent.com/events/national-diagnostic-imaging-symposium-2012/event-summary-d9ca77152935404ebf0404a0898e13e9. aspx

Asian Pacific Digestive Week 2012 5/12/2012 to 8/12/2012 Location: Bangkok, Thailand Tel: (66) 2 748 7881 ext. 111 Fax: (66) 2 748 7880 E-mail: [email protected] Website: www.apdw2012.org

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

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July 2012

After Hours

Chengdu Land of Tea ,

Tao& Pandas

Chengdu epitomizes today’s China – modern, yet historical and quaint. Leonard Yap writes.

C

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

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

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July 2012

After Hours

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

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

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July 2012

Humor

“Take it easy!”

“What a pleasant surprise for a change. With all the hypochondriacs coming here, it’s nice to see someone who’s actually sick!”

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

“We are gonna have to open you up again. My colleague can’t find his wedding ring!”

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