Analisis Efektivitas Biaya Kombinasi Obat Antihipertensi Pada Pasien Rawat Inap Di RS PKU Muhammadiyah Yogyakarta Tahun 2020

Terapi kombinasi disarankan pada pasien hipertensi yang memiliki tekanan darah tidak terkontrol dengan terapi tunggal. Biaya pengobatan semakin meningkat setiap tahunnya. Penelitian ini bertujuan untuk mengetahui terapi kombinasi obat antihipertensi yang paling cost effective pada pasien rawat inap RS PKU Muhammadiyah Yogyakarta tahun 2020. Penelitian ini merupakan penelitian deskriptif dengan pendekatan analisis farmakoekonomi metode Cost Effectiveness Analysis (CEA) yang dilakukan secara retrospektif. Teknik pengambilan sampel yang digunakan adalah total sampling. Data dikelompokkan berdasarkan pola terapi pasien kemudian dilakukan analisis berdasarkan ACER dan ICER. Jenis pola terapi kombinasi antihipertensi yang paling banyak digunakan adalah kombinasi dua obat (53%). Terapi dengan ACER terendah yaitu Diuretika + ARB + β Bloker (Rp. 15.257). Hasil ICER kombinasi ACEI + CCB + β Bloker + Diuretikb + Agonis α2 Sentral + ACEI memiliki nilai yang terendah dengan Rp. 25.353 jika dibandingkan dengan terapi standar. Namun, terapi CCB + β Bloker, Diuretika + ACEI + CCB, Diuretika + ARB + β Bloker, ARB + CCB + β Bloker + Agonis α2 Sentral bersifat dominan terhadap terapi standar pada cost effectiveness grid. Sehingga, terapi yang paling cost effective berdasarkan ACER dan ICER adalah Diuretika + ARB + β Bloker.Combination therapy is recommended in hypertensive patients whose blood pressure is not controlled by monotherapy. Medical expenses are increasing every year. This study aims to determine the most cost-effective antihypertensive drug combination therapy for inpatients at PKU Muhammadiyah Yogyakarta Hospital in 2020. This study is a descriptive study with a pharmacoeconomic analysis approach using the Cost-Effectiveness Analysis (CEA) method which was carried out retrospectively. The sampling technique used is total sampling. The data were grouped based on the patient's therapy pattern and then analyzed based on ACER and ICER. The most widely used combination antihypertensive therapy pattern was a combination of two drugs (53%). The therapy with the lowest ACER was Diuretica + ARB + Blockers (Rp. 15.257). The ICER result of the combination of ACEI + CCB + Blocker + Diureticb + Central α2 Agonist + ACEI has the lowest value with Rp. 25,353 when compared to standard therapy. However, CCB + Blocker, Diuretica + ACEI + CCB, Diuretic + ARB + Blocker, ARB + CCB + Blocker + Central α2 Agonist are dominant over standard therapy on the cost-effectiveness grid. Thus, the most cost-effective therapy based on ACER and ICER is Diuretica + ARB + Blockers.

Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.

The very early tumor regression rate and safety of anlotinib combined with sintilimab and chemotherapy for advanced non-small cell lung cancer without driver mutations.

e21090 Background: Unlike bevacizumab, anlotinib, which is also an anti-angiogenic drug, is indicated for lung squamous cell carcinoma(LSCC). A phase IB study showed that the first-line therapy with anlotinib and sintilimab for stage IIIB to IV NSCLC with negative driver genes has the objective response rate of 72.7%. Regardless of the PD-1 expression level, this combination method has consistent therapeutic benefit. According to the IMpower150 study, the four-drug combination therapy has a synergistic effect and prolong the survival time. It is necessary to further explore the efficacy and safety of anlotinib combined with sintilimab and chemotherapy for NSCLC without driver mutations. Methods: We retrospectively analyzed the patients of newly diagnosed unresectable stage IIIA-IVB NSCLC who received platinum-containing dual-drug chemotherapy combined with anlotinib and sintilimab in our hospital from January 2019 to December 2020. Patients receive at least one cycle of treatment, and the efficacy can be evaluated. The main observation indicators are the very early tumor regression rate and the safety. Results: This study included 11 patients with stage IIIA-IVB NSCLC with no driver mutations that were not resectable. Ten patients (90.9%) were male, with a median age of 65 years. The pathological types were LSCC (7, 63.6%), lung adenocarcinoma (3, 27.3%), and poor differentiated carcinoma (1, 9.1%). Six patients were with stage ⅢA-ⅢB, 4 patient with ⅢC-IVB. Eleven patients received an average of 1.63 cycles of treatment. In order to evaluate the efficacy of multi-drug combination therapy in a timely manner, and effectively avoid the risk of hemoptysis caused by anlotinib-induced pulmonary cavity, all patients were evaluated for efficacy after receiving one cycle of treatment. Eight patients achieved very early tumor regression (defined as tumor shrinkage ≥30% after receiving one cycle of treatment in the evaluation of efficacy), 2 patients achieved stable disease, and 1 patients achieved disease progression. The very early tumor regression rate was 72.7%. Three patients with locally advanced (ⅢA-ⅢB) NSCLC underwent radical R0 resection and the downstage rate reached 100%; 2 patients underwent radical radiotherapy. At the last follow-up time in February 2021, one patient died, the remaining patients were alive. No treatment-related grade 3-4 adverse reactions were observed. Conclusions: The high rate of very early tumor regressions in inoperable locally advanced NSCLC provided opportunities for radical surgery and radiotherapy in a short period of time. And the safety is satisfactory. Therefore, our research group has registered the prospective study of anlotinib combined with sintilimab and chemotherapy for the neoadjuvant downstage treatment of stage III NSCLC (Registration number: ChiCTR1900026631).

Optimizing Combinatory Drugs using Markov Chain-Based Models

Background: Combinatory drug therapy for complex diseases, such as HSV infection and cancers, has a more significant efficacy than single-drug treatment. However, one key challenge is how to effectively and efficiently determine the optimal concentrations of combinatory drugs because the number of drug combinations increases exponentially with the types of drugs. Results: In this study, a searching method based on Markov chain is presented to optimize the combinatory drug concentrations. Its performance is compared with four stochastic optimization algorithms as benchmark methods by simulation and biological experiements. Both simulation results and experimental data demonstrate that the Markov Chain-based approach is more reliable and efficient than the benchmark algorithms.Conclusion: This article provides a versatile method for combinatory drug screening, which is of great significance for clinical drug combination therapy.

The Effectiveness of Varying Combination Ratios of A. cordifolia and M. indica against Field and Laboratory Strains of P. falciparum In Vitro

Background. Drug resistance in malaria is a global problem, with reports of Plasmodium parasites resistant to the current first-line antimalarial drug, artemisinin, expanding from Southeast Asia to Africa. There is therefore an urgent need to identify new drug candidates that will be effective against the existing malaria parasites. Drug combination therapy presents a myriad of advantages over monotherapy including delayed onset of resistance, potentiation, and synergism. This present study explored the effectiveness of combinations of aqueous extracts of Alchornea cordifolia (A. cordifolia) and Mangifera indica (M. indica) at clearing both laboratory and field isolates of P. falciparum. Methods. Synchronized ring stage cultures of field (FA08) and laboratory strains (NF54 and CamWT_C580Y) of P. falciparum were subjected to combinations of different concentrations and ratios of aqueous extracts of A. cordifolia and M. indica. The growth inhibition of the individual plant extracts and their combinatory effects were studied in vitro using SYBR Green I drug assay. Results. The A. cordifolia extract exhibited 50% inhibitory concentration (IC50) of 2.71, 7.80, and 3.56 μg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Mangifera indica exhibited IC50 of 18.11, 20.08, and 10.23 μg/mL against the NF54, CamWT_C580Y, and FA08 parasite strains, respectively. Additive, synergistic and antagonistic interactions were observed at different combinations of A. cordifolia and M. indica extracts. Conclusion. A combination product containing A. cordifolia and M. indica has the potential to serve as an effective antimalarial as majority of the tested combinations of aqueous extracts of A. cordifolia and M. indica extracts exhibited synergistic effects in vitro against the NF54, CamWT_C580Y, and FA08 P. falciparum strains.