Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy.

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy

Purification and Characterization of Recombinant Darbepoetin Alfa from Leishmania tarentolae

Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer chemotherapy. We herein describe the structural characterization of recombinant darbepoetin alfa produced by Leishmania tarentolae T7-TR host. The DNA expression cassette was integrated into the L. tarentolae genome through homologous recombination. Transformed clones were selected by antibiotic resistance, diagnostic PCRs, and protein expression analysis. The structure of recombinant darbepoetin alfa was analyzed by isoelectric focusing, ultraviolet–visible spectrum, and circular dichroism (CD) spectroscopy. Expression analysis showed the presence of a protein band at 40 kDa, and its expression level was 51.2 mg/ml of culture medium. Darbepoetin alfa have 5 isoforms with varying degree of sialylation. The UV absorption and CD spectra were analogous to original drug (Aranesp), which confirmed that the produced protein was darbepoetin alfa. Potency test results revealed that the purified protein was biologically active. In brief, the structural and biological characteristics of expressed darbepoetin alfa were very similar to Aranesp which has been normally expressed in CHO. Our data also suggest that produced protein has potential to be developed for clinical use. © 2016, Springer Science+Business Media New York

Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast cancer : randomized clinical trial

BACKGROUND: The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm. METHODS: One thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided. RESULTS: Epoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs -2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse. CONCLUSIONS: Epoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis

Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.

Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB-06-002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB-06-002 who continued receiving taliglucerase alfa in extension Study PB-06-003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB-06-003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30-33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, -1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), -19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, -51.5% (±8.1%; n = 10); and CCL18 concentration, -36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment-related adverse events were mild or moderate and transient. The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661-665, 2016. © 2016 Wiley Periodicals, Inc

Cloning and expression of codon-optimized recombinant darbepoetin alfa in Leishmania tarentolae T7-TR

Darbepoetin alfa is an engineered and hyperglycosylated analog of recombinant human erythropoietin (EPO) which is used as a drug in treating anemia in patients with chronic kidney failure and cancer. This study desribes the secretory expression of a codon-optimized recombinant form of darbepoetin alfa in Leishmania tarentolae T7-TR. Synthetic codon-optimized gene was amplified by PCR and cloned into the pLEXSY-I-blecherry3 vector. The resultant expression vector, pLEXSYDarbo, was purified, digested, and electroporated into the L. tarentolae. Expression of recombinant darbepoetin alfa was evaluated by ELISA, reverse-transcription PCR (RT-PCR), Western blotting, and biological activity. After codon optimization, codon adaptation index (CAI) of the gene raised from 0.50 to 0.99 and its GC content changed from 56 to 58. Expression analysis confirmed the presence of a protein band at 40 kDa. Furthermore, reticulocyte experiment results revealed that the activity of expressed darbepoetin alfa was similar to that of its equivalent expressed in Chinese hamster ovary (CHO) cells. These data suggested that the codon optimization and expression in L. tarentolae host provided an efficient approach for high level expression of darbepoetin alfa. © 2015 Elsevier Ltd. All rights reserved

UPAYA PESANTREN DALAM MEWUJUDKAN KELUARGA SAKINAH (STUDI KASUS DI YAYASAN PONPES SPMAA TURI LAMONGAN)

The sakinah family is an important thing that must be owned by every married couple in the household, the purpose of realizing a sakinah family is to create a sense of peace and comfort in the family. The development of the times affects a person's mindset and lifestyle, especially among teenagers in the concept of marriage. For this reason, Islamic boarding schools are here to bring the concept of thinking as a result of exemplary steps in realizing a sakinah family. The author conducted research on the efforts, and implementation of Islamic boarding schools in realizing a sakinah family at the SPMAA Turi Lamongan Islamic Boarding School Foundation. In data collection techniques, researchers used interviews, observation and documentation. The results of this study focus on the efforts and implementation of Islamic boarding schools in realizing a sakinah family at the SPMAA Turi Lamongan Islamic Boarding School Foundation Kata kunci: Upaya Pesantren, Mewujudkan, Keluarga Sakina

FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN KEMAUAN KELUARGA DALAM MEMBAYAR TARIF PELAYANAN RAWAT JALAN DI PUSKESMAS CILACAP SELATAN I KABUPATEN CILACAP TAHUN 2005

Permintan terhadap pelayanan kesehatan akan meningkat jika kendala biaya yang ada telah dapat di atasi dengan baik.Kecermatan menerapkan besarnya tarif memegang peranan penting (income),apabila ternyata besarnya tarif lebih rendah dari total pengeluaran pasti yang dapat menimbulkan kesulitan. Pernelitian bertujuan mengetahui faktor-faktor yang berhubungsn dengan kemauan keluarga dengan membayar tarif pelayanan rawat jalan di Puskesmas Cilacap Selatan.Penelitian termasuk penelitian survai dengan metode pendekatan cros sectional.Responden penelitian adalah kepala keluarga bukan peserta askes,non gakin sebagai pengambil keputusan dalam keluarga yang pernah berobat jalan di Puskesmas Cilacap Selatan I sebanyak 100 orang .Metode analis data menggunakan uji statistik Kendall Tau-c. Kesimpulan hasil penelitian : 1)Ada hubungan yang bermakna antara kebutuhan pelayanan rawat jalan dengan kemauan membayar tarif pelayanan.Hasil analisi statistik di peroleh nilai p = 0,011 yang lebih kecil dari alfa = 0,05. 2)Ada hubungan yang bermakna antara sikap terhadap pelayanan rawat jalan dengan kemauan membayar tarif pelayanan.Hasil analisis statistik di peroleh nilai p = 0,001yang lebih kecil dari alfa = 0,05. 3)Ada hubungan yang bermakna antara pengetahuan tentang pelayanan rawat rawat jalan dengan kemauan membayar tarif pelayanan.Hasil analisis statistik di peroleh nilai p = 0,010 yang lebih kecil dari alfa = 0,05. 4)Ada hubungan yang bermakna antara pendapatan keluarga per kapita dengan kemauan membayar tarif pelayanan.Hasil analisis statistik diperoleh nilai p =0,0001 yang lebih kecil dari alfa = 0,05. 5)Ada hubungan yang bermakna antara biaya pelayanan rawat jalan dengan kemauan membayar tarif pelayanan. Hasil analisis statistik diperoleh nilai p =0,035 yang lebih kecil dari alfa =0,05. 6)Ada hubungan yang bermakna antara lama waktu menunggu pelayanan rawat jalan dengan kemauan membayar tarif pelayanan. Hasil analisis statistik diperoleh nilai p = 0,010 yang lebih kecil dari alfa = 0,05. 7)Ada hubungan yang bermakna antara jarak pelayanan rawat jalan dengan kemauan membayar tarif pelayanan . Hasil analisis statistik diperoleh nilai p = 0,227 yang lebih kecil dari alfa = 0,05. Kata Kunci: Pasien Rawat Jalan Puskesmas, Kemauan Membayar Tarif SOME FAKTORS RELATED TO THE WILLINGNESS TO PAY THE OUTPATIENT SERVICE OF CILACAP SELATAN I PUBLIC HEALT CENTER IN CILACAP REGENCY YEAR 2005 Request to health service will mount if existing expence constraint has earned in overcoming better. Apply the level of tariff play a part important (income), if in the reality the level of lower tariff from totalizing sure expenditure which can generate the research difficulty aim to know the faktors of wich deal with family willingness to pay service of cilacap Selatan I Public Health Center.This research is inclusive of research survay with the method of approach of cross sectional.Research responder is family head non-competitor ,non-pureas decision taker in family,which have medicine walker in Cilacap Selatan I Public Health Center as much 100 people.Method analyzes the data use the statistical Test of Kendall Tau-C. Result of research 1)There is relation having a meaning between service requirement take care with willingness to pay service. Result of statistical analysis obtained by value p = 0,011 which is smaller than alfa = 0,05. 2)There is relation having a meaning between attitude to service take care with the willingness to pay service.Result of statistical analysis obtained by value p = 0,001 which is smaller than alfa = 0,05. 3)There is relation having a meaning between knoledge about service take care with the willingness to pay service. Result of statistical analysis obtained by value p = 0,010 which is smaller than alfa = 0,05. 4)There is relation having a meaning between family earnings per capita with the willingness to pay service.Result of statistical analysis obtained by value p = 0,0001 which is smaller than alfa = 0,05. 5)There is relation having a meaning between service expence take care with the willingness to pay service.Result of statistical analysis obtained by value p = 0,035 which is smaller than alfa = 0,05. 6) There is relation having a meaning between time depth awaith the service take care with the willingness to pay service. Result of statistical analysis obtained by value p =0,010 which is a smaller than alfa = 0,05. 7)there is not relation having a meaning between service distance take care with the willingness to pay service. Result of statistical analysis obtained by value p = 0,227 which is smaller than alfa = 0,05. Keyword : Out patient Puskesmas ,Willingness To Pa