Iwan Dwiprahasto

Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics

Objective Nausea and vomiting are the most distressful side effects of cytotoxic drugs in cancer patients. Antiemetics are commonly used to reduce these side effects. However, the current antiemetic efficacy is about 70–80% in patients treated with highly-emetogenic cytotoxic drugs. One of the potential factors explaining this suboptimal response is variability in genes encoding enzymes and proteins which play a role in metabolism, transport and receptors related to antiemetic drugs. Aim of this review was to describe the pharmacology and pharmacogenetic concepts of of antiemetics in oncology. Method Pharmacogenetic and pharmacology studies of antiemetics in oncology published between January 1997 and February 2010 were searched in PubMed. Furthermore, related textbooks were also used for exploring the pharmacology of antiemetic drugs. The antiemetic drugs which were searched were the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs), dopamine antagonists, corticosteroids, benzodiazepines, cannabinoids, antihistamines and neurokinin-1 antagonists. Result The 5-HT3RAs are widely used in highly emetogenic chemotherapy in combination with dexamethasone and a neurokinin-1 antagonist, especially in acute phase. However, the dopamine antagonists and benzodiazepines were found more appropriate for use in breakthrough and anticipatory symptoms or in preventing the delayed phase of chemotherapy induced nausea and vomiting. The use of cannabinoids and antihistamines need further investigation. Only six articles on pharmacogenetics of the 5-HT3RAs in highly emetogenic chemotherapy are published. Specifically, these studies investigated the association of the efficacy of 5-HT3RAs and variants in the multi drug resistance 1 (MDR1) gene, 5-HT3A,B and C receptor genes and CYP2D6 gene. The pharmacogenetic studies of the other antiemetics were not found in this review. Conclusion It is concluded that pharmacogenetic studies with antiemetics are sparse. It is too early to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice: confirmation of early findings is required.

Translation and Validation of EORTC QLQ-C30 into Indonesian Version for Cancer Patients in Indonesia

OBJECTIVE Quality of life studies in Indonesia are still uncommon. This research was aimed to validate the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 in Indonesian version. The standard procedure of forward-backward translation was adhered to in the translation procedures. The validity procedure included reliability, convergent and discriminant validity, known-groups validity, factor analysis and external convergent validity. METHODS Data were collected from cancer patients in the Oncology Department of Sardjito Hospital, Yogyakarta, Indonesia, who were treated with cisplatin at the dosage ≥50 mg/m(2) as monotherapy or in combinations. The Short Form-36 was used to assess the external convergent validity of our translated questionnaire. RESULTS One hundred and twenty-eight patients were recruited from March 2009 to November 2009. The internal consistency with values of >0.70 was observed in the Indonesian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scales. All items in the questionnaire met the criteria of convergent and discriminant validity, except for items 5. Both of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and the Short Form-36 showed that different diagnoses were associated with a similar impact on quality of life. Factor analysis showed that only the role function and social function loaded onto the second factor together. Correlations between the Indonesian versions of both questionnaires were moderate: between 0.18 and 0.48 for the physical, emotional, social, fatigue and pain domains. CONCLUSIONS The Indonesian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 can be used as a questionnaire to assess quality of life in Indonesian cancer patients with high-emetogenic treatments.

The Administration to Indonesians of Monosodium l-Glutamate in Indonesian Foods: An Assessment of Adverse Reactions in a Randomized Double-Blind, Crossover, Placebo-Controlled Study

Monosodium L-glutamate (MSG) has been suggested to cause postprandial symptoms after the ingestion of Chinese or oriental meals. Therefore, we examined whether such symptoms could be elicited in Indonesians ingesting levels of MSG typically found in Indonesian cuisine. Healthy volunteers (n = 52) were treated with capsules of placebo or MSG (1.5 and 3.0 g/person) as part of a standardized Indonesian breakfast. The study used a rigorous, randomized, double-blind, crossover design. The occurrence of symptoms after MSG ingestion did not differ from that after consumption of the placebo.

Impact of Chemotherapy-Induced Nausea and Vomiting on Quality of Life in Indonesian Patients With Gynecologic Cancer

Background Quality of life (QoL) has become a major outcome in the treatment of patients with cancer. This study is aimed at examining the impact of chemotherapy-induced nausea and vomiting on QoL of patients with gynecologic cancer in Indonesia. Methods Chemotherapy-naive patients with gynecologic cancer, who were treated with cisplatin at a dosage 50 mg/m2 or higher as monotherapy or as part of combination chemotherapy regimens, were recruited in the Oncology Department, Dr. Sardjito Hospital, Yogyakarta, Indonesia. Quality of life was assessed by using the Indonesian version of the European Organization for Research and Treatment for Cancer of Quality of Life Questionnaire and Short Form-36, administered immediately before and on day 5 after chemotherapy administration. Patients used a daily diary to record nausea and vomiting during 5 days after chemotherapy. Results Most (74.9%) of the 179 patients experienced delayed emesis during the 5 days after chemotherapy despite prophylactic use of antiemetics. The delayed nausea and emesis caused significant negative impact on patients’ QoL. Nausea in the delayed phase caused negative effects on patients’ QoL. Conclusions Patients reported a negative impact on the QoL of delayed emesis after chemotherapy. Poor prophylaxis of patients’ nausea and vomiting after chemotherapy interferes with patients’ QoL. Medical and behavioral interventions may help to alleviate the negative consequences of chemotherapeutic treatment in patients with gynecologic cancers treated with suboptimal antiemetics.

METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS COLONIZATION AND SCREENING METHOD EFFECTIVENESS FOR PATIENTS ADMITTED TO THE INTENSIVE CARE

Methicillin-resistant S.aureus (MRSA) menyebabkan banyak infeksi nosokomial (inos) dan penyebarannya menunjukkan mutu clean care. Kejadian inos MRSA meningkatkan angka kesakitan, kematian, lama rawat inap, kebutuhan antibiotika dan meluasnya resistensi, readmisi serta biaya kesehatan. Penapisan kolonisasi MRSA di pasien yang akan dirawat intensif diperlukan untuk mencegah penyebaran dan mengendalikan peresepan antibiotika. Pemeriksaannya diharapkan tepat guna untuk mendukung Sistem Jaminan Kesehatan Nasional. Penelitian dilaksanakan di Ruang Rawat Intensif RSUP Dr Sardjito Yogyakarta di seluruh pasien pada tahun 2015 saat masuk sesuai patokan kesertaan dan non-kesertaan. Spesimen dari nares anterior dan kulit (aksila-inguinal), diambil dalam 1x24 jam, dinilai kepositifan MRSA menggunakan beberapa media identifikasi di Instalasi Laboratorium Klinik. Perbandingan analitik dan praktikabilitas metode identifikasi dianalisis efektivitasnya. Kejadian kolonisasi S.aureus dan MRSA di pasien saat masuk perawatan Ruang Intensif 23,4% dan 9,7%. Faktor kebahayaan dominan kolonisasi MRSA adalah riwayat perawatan RS. Nares anterior dominan sebagai tempat kolonisasi S.aureus (74,2%) dan MRSA (33,7%). Terdapat 7,7% kolonisasi lolos deteksi bila sampling hanya dilakukan di nares. Kesepakatan hasil pemeriksaan antar metode baik (indeks Kappa >0,8) dengan metode yang disarankan adalah penggunaan media selektif MRSA langsung atau urutan metode deteksi menggunakan Blood Agar, pengecatan Gram, uji aglutinasi, media khromogenik selektif MRSA. Metode penapisan dengan tingkat deteksi dan praktikabilitas yang baik bermanfaat mendukung pengendalian infeksi di ruang berkebahayaan tinggi.

PHYLOGENETIC PROFILE OF ESCHERICHIA COLI CAUSING BLOODSTREAM INFECTION AND ITS CLINICAL ASPECT

Escherchia coli merupakan satu dari bakteri yang paling sering ditemukan dalam infeksi aliran darah. Tujuan penelitian ini adalah untuk mengeksplorasi profil filogenetik E. coli yang menyebabkan infeksi aliran darah dan aspek klinisnya. Ini merupakan penelitian observasional yang melibatkan 12 subjek yang menderita infeksi aliran darah yang disebabkan oleh E.coli. Isolat klinis E.coli serta hasil uji kepekaan antimikroba diperoleh dari metode kaldu microdilution otomatis. Data klinis diperoleh dari rekam medis dan analisis filogenetik yang dilakukan dengan polymerase chain reaction menggunakan gena chuA dan YjaA. Data dianalisis dengan menggunakan statistik deskriptif. Sumber infeksi ini berasal dari saluran kemih, paru-paru, saluran pencernaan dan kulit yang ditemukan dalam 7 kasus. Namun, sumber infeksi tidak diketahui dalam 5 kasus. Sebagian besar subjek adalah pria dewasa dengan keganasan sebagai penyakit yang mendasarinya. Escherichia coli sebagai etiologi infeksi aliran darah sebagian besar (75%) menghasilkan enzim ESBL dan resistensinya terhadap antimikroba seperti ampicilin, ampicilin/sulbactam, ceftazidime, ceftriaxon, cefepime, aztreonam, ciprofloxacin dan trimetropim-sulfamethoxazol yang cukup tinggi. Kelompok filogenetik dari isolat klinis ini sebagian besar (75%) adalah grup B2 dan grup D yang dikenal sebagai strain virulen ekstraintestinal. Isolat klinis yang tersisa (25%) dapat digolongkan sebagai kelompok filogenetik A atau B1 dimana kelompok A dikenal sebagai strain komensal.

KESAHIHAN DIAGNOSTIK HEMOGLOBIN RETIKULOSIT UNTUK DETEKSI DEFISIENSI ZAT BESI DI KEHAMILAN (Diagnostic Validity of Reticulocyte Hemoglobin for Iron Deficiency Detection in Pregnancy)

Entering the second trimester of pregnancy, more iron is required due to the increase in erythrocyte mass, plasma volume and the development of fetus as well as chorion. Iron is needed the most in the third trimester. The existing hematological iron stage parameters can only detect iron deficiency in the latest stage. The aim of this study was to know the assessment validity of Ret-He examination as a new parameter to diagnose iron deficiency in pregnant women with anemia, as well as a screening tool for those in term pregnancy without anemia. The research design was cross sectional. The subjects were women in term pregnancy, gathered from PKU Muhammadiyah Hospital, Bantul Yogyakarta from May to November 2013. A seven (7) mL blood sample was taken from the cubital vein of the subjects. Two mL of the sample was tested for routine hematological examination using an EDTA tube, while the Ret-He was assessed using an automatic hematological instrument Sysmex XT-2000-i (Symex Corporation, Kobe, Japan). The serum of the remaining five (5) mL was used to check the serum iron and TIBC to obtain the saturation value (Tsat) using Cobas analyzer C501 (Roche Diagnostics, Germany), while the serum ferritin (SF) was examined using Minividas. The subjects were classified into two (2) groups based on the Hb levels, namely: anemia (Hb<11 g/dL) and those who did not (Hb≥11 g/dL). Furthermore, they were also classified into two (2) groups based on transferrin saturation values: iron deficient (Tsat <9%) and normal (Tsat ≥9%). From 291 subjects, 59 (20.3%) were found to have anemia and 232 (79.7%) did not. The cut off value of Ret-He to diagnose iron deficiency in pregnant women with anemia was 29.8 pg (82% sensitivity and 72% specificity). Meanwhile, the cut-off value of Ret-He for iron deficiency screening in pregnant women without anemia was 29.8 pg, with a sensitivity and specificity of 92% and 87% respectively. The Ret-He holds a good diagnostic validity to detect iron deficiency in pregnancy, with or without anemia.

The Development of Quality of Life Questionnaire for Indonesian Breast Cancer Patients: INA-BCHRQoL

Introduction: The breast cancer related incidence and mortality rate in Indonesia are included in the top 10 and top 5 highest in the world. A country-specific Health Related Quality of Life measurement tool is required to help clinician observe and improve the management of the disease. Methods: We developed the questionnaire, namely Indonesian Breast Cancer Health Related Quality of Life (INA-BCHRQoL) by incorporating not only the generic variables such as physical, psychological, and social; but also spiritual variable which is suitable for Indonesian population. The questionnaire was validated to the same population using the value of corrected item-total correlation and the value of Cronbach Alpha. Results: Fourty three questions were considerably valid and reliable on evaluating the HRQoL of early state of breast cancer patients in Indonesia as the value of Cronbach Alpha for physical, cognitive, social and spiritual domain were higher than 0.8 and the corrected item-total correlation were also higher than 0.3. Each domain of the questionnaire was not influenced by the treatment options. Twenty four early stage breast cancer (10 FAC based chemotherapy and 14 Taxan based chemotherapy) were enrolled in the main study and the score of HRQOL obtained from INA-BCHRQoL were considerably high. Conclussion: The INA-BCHRQoL questionnaire can be implemented as a valid and reliable tool to assess quality of life in early stage breast cancer patients in Indonesia.

Compliance Pengguna Antihipertensi di RSUP DR. SARDJITO Yogyakarta (Periode Juli 2006- Juni 2009)

Hypertension is the second largest of the 10 diseases on an outpatient at a hospital in Indonesia. The poor compliance to therapy of hypertension is a major cause of uncontrolled blood pressure. The aim of this study is to determine compliance antihypertension on patient at DR. Sardjito hospital Yogyakarta. This study was designed with a retrospective cohort study design using a database of participants claimed prescribing health insurance (ASKES) in the DR. Sardjito hospital using antihypertensive drugs. Compliance measured with medication possession ratio (MPR). Data was analysed by chi- square and logistic regression statistic. From 8.011 patients, compliance of antihypertensive drugs during the first year is 7,6%. Analysis for compliance showed that the type of antihypertensive diuretics are more compliance compare with angiotensin II receptor blockers, ACE inhibitors, calcium channel blockers and beta blockers. Combination therapy (20,7%) is more compliance than monotherapy ( 4,1%), as well as drugs administration 1 time a day (8,2%) is more compliance than drug administration 2 times (2,5%) and 3 times a day (3%). The proportion of compliance in antihypertensive users at DR. Sardjito hospital classified as less good. Compliance pattern indicates that therapy is not continuous, the longer the use of antihypertensive therapy, the higher the discontinuous therapy.

KEPATUHAN PENGGUNAAN ANTIHIPERTENSI SEBAGAI PREDIKTOR LAJU KEJADIAN DAN BIAYA RAWAT INAP

Persistensi penggunaan antihipertensi pada pasien hipertensi sangat diperlukan. Mengingat luaran utama dari terapi hipertensi adalah menurunkan atau mencegah terjadinya kejadian penyakit kardiovaskular seperti infark miokard, stroke yang berujung pada risiko kematian. Penelitian ini bertujuan untuk mengevaluasi dampak klinis berupa laju kejadian dan biaya rawat inap pada kelompok pasien hipertensi yang persisten dan tidak persisten menggunakan obat antihipertensi berdasarkan klaim resep pengobatan PT Askes (Persero). Rancangan penelitian yang digunakan adalah studi kohort retrospektif dengan menggunakan basis data pasien hipertensi rawat jalan peserta asuransi kesehatan PT Askes (Persero) di RSUD Panembahan Senopati Bantul. Jumlah subjek yang ikut dalam penelitian ini sebanyak 304 pasien hipertensi yang menggunakan obat antihipertensi pertama kali (tanggal indeks pengobatan 1 Juli 2007 – 31 Desember 2008). Analisis data yang digunakan pada penelitian ini, antara lain uji khi kuadrat, analisis kesintasan Kaplan-Meier, dan cox proportion hazard test . Setelah dilakukan pengamatan berkisar 3 sampai 4,5 tahun bahwa laju kejadian rawat inap pada pasien yang persisten menggunakan antihipertensi lebih lambat dan bermakna secara statistik daripada pasien hipertensi yang tidak persisten menggunakan antihipertensi (HR= 0,12; IK 95%= 0,006-0,23). Rata-rata biaya untuk mengatasi luaran klinis berupa rawat inap pada kelompok pasien yang persisten menggunakan antihipertensi (Rp. 2.758.109,28) lebih rendah daripada kelompok pasien hipertensi yang tidak persisten menggunakan antihipertensi dan dirawat inap (Rp. 4.125.412,00). Kesimpulan dari penelitian ini adalah peningkatan persistensi penggunaan antihipertensi pada pasien hipertensi dapat menekan laju kejadian dan biaya rawat inap. Kata kunci : persistensi, hipertensi, kejadian rawat inap, biaya