Cost-Effectiveness of Cerebrolysin after Ischemic Stroke: Secondary Analysis of the CARS Study.

The cost-effectiveness of Cerebrolysin as an add-on therapy for moderate-severe acute ischemic stroke is a topic that remains understudied. This study aims to address this gap by performing a comprehensive cost-utility analysis using both deterministic and probabilistic methods from a payer perspective and within the Romanian inpatient care setting. Quality-adjusted life years (QALYs) were calculated using partial individual patient data from the 2016 Cerebrolysin and Recovery After Stroke (CARS) trial, utilizing three different health state valuation models. Cost data was extracted from actual acute care costs reported by Romanian public hospitals for reimbursement purposes for patients included in the CARS study. Incremental cost-effectiveness ratios were calculated for each treatment arm for the duration of the clinical trial. Deterministic analysis based on sample mean values indicates Cerebrolysin would be cost-effective at a threshold between roughly 18.8 and 29.9 thousand EUR, depending on valuation techniques. Probabilistic sensitivity analysis results indicate an 80% chance probability of cost-effectiveness of Cerebrolysin as an add-on therapy for acute ischemic stroke, considering a willingness-to-pay threshold of 50,000 EUR in a 90-day timeframe after stroke. Further economic evaluations of Cerebrolysin are needed to strengthen these findings, covering a timeframe of at least 12 months after the acute incident, which would account for treatment effects spanning beyond the first 90 days after ischemic stroke. These should be conducted to determine its cost-effectiveness under various care settings and patient pathways. Most importantly, modelling techniques are needed to answer important questions such as the estimates of population gain in QALYs after acute administration of Cerebrolysin and the potential offsetting of direct medical costs as a result of administering the intervention.

A five-year (2017-2021) time series evaluation of patient-reported informal healthcare payments in Romania.

Low wages of health professionals are widely recognized as one of the drivers of informal payments in Romania's healthcare system. In January 2018, the government increased wages by an average of 70% to 172% in the public healthcare sector. This study examined the trends in patient-reported informal healthcare payments, discussing the effect of a one-time wage increase in 2018 and the impact of the COVID-19 pandemic in 2020 and 2021. It draws on monthly survey data of patient-reported informal payments collected between January 2017 and December 2021. We analyzed three periods: before the wage rise ("low pay"), between the wage rise and the COVID-19 pandemic ("high pay"), and during the COVID-19 pandemic. We found that patient-reported informal payments decreased between the "low pay" and "high pay" period but with a sharper decline during the COVID-19 pandemic. The share of respondents willing to report informal payments increased during the "high pay" period, indicating a stronger willingness to voice dissatisfaction with health services and informal payments, but slowed down during the first lockdown in 2020. Informal payments were more frequently reported in larger hospitals and the poorest geographical areas. While the 2018 wage increase may have contributed to less prevalent informal payments, survey coverage and design must be improved to draw robust, system-level conclusions to inform tailored policy actions.

The economic burden of stroke: a systematic review of cost of illness studies.

Stroke is one of the leading causes of morbidity and mortality worldwide. As the number of stroke cases is rising from one year to another, policymakers require data on the amount spent on stroke to enforce better financing policies for prevention, hospital care, outpatient rehabilitation services and social services. We aimed to systematically assess the economic burden of stroke at global level. Cost of stroke studies were retrieved from five databases. We retrieved the average cost per patient, where specified, or estimated it using a top-down approach. Resulting costs were grouped in two main categories: per patient per year and per patient lifetime. We extracted information from forty-six cost of illness studies. Per patient per year costs are larger in high income countries and in studies conducted from the payer perspective. The highest average per patient per year cost by country was reported in the United States ($59,900), followed by Sweden ($52,725) and Spain ($41,950). The highest per patient lifetime costs were reported in Australia ($232,100) for all identified definitions of stroke. Existing literature regarding the economic burden of stroke is concentrated in high-income settings, with very few studies conducted in South America and Africa. Published manuscripts on this topic highlight substantial methodological heterogeneity, rendering comparisons difficult or impossible, even within the same country or among studies with similar costing perspectives.

A fluorescence anisotropy method for measuring protein concentration in complex cell culture media.

The rapid, quantitative analysis of the complex cell culture media used in biopharmaceutical manufacturing is of critical importance. Requirements for cell culture media composition profiling, or changes in specific analyte concentrations (e.g. amino acids in the media or product protein in the bioprocess broth) often necessitate the use of complicated analytical methods and extensive sample handling. Rapid spectroscopic methods like multi-dimensional fluorescence (MDF) spectroscopy have been successfully applied for the routine determination of compositional changes in cell culture media and bioprocess broths. Quantifying macromolecules in cell culture media is a specific challenge as there is a need to implement measurements rapidly on the prepared media. However, the use of standard fluorescence spectroscopy is complicated by the emission overlap from many media components. Here, we demonstrate how combining anisotropy measurements with standard total synchronous fluorescence spectroscopy (TSFS) provides a rapid, accurate quantitation method for cell culture media. Anisotropy provides emission resolution between large and small fluorophores while TSFS provides a robust measurement space. Model cell culture media was prepared using yeastolate (2.5 mg mL(-1)) spiked with bovine serum albumin (0 to 5 mg mL(-1)). Using this method, protein emission is clearly discriminated from background yeastolate emission, allowing for accurate bovine serum albumin (BSA) quantification over a 0.1 to 4.0 mg mL(-1) range with a limit of detection (LOD) of 13.8 µg mL(-1).

Chemical & RNAi screening at MSKCC: a collaborative platform to discover & repurpose drugs to fight disease.

Memorial Sloan Kettering Cancer Center (MSKCC) has implemented the creation of a full service state-of-the-art High-throughput Screening Core Facility (HTSCF) equipped with modern robotics and custom-built screening data management resources to rapidly store and query chemical and RNAi screening data outputs. The mission of the facility is to provide oncology clinicians and researchers alike with access to cost-effective HTS solutions for both chemical and RNAi screening, with an ultimate goal of novel target identification and drug discovery. HTSCF was established in 2003 to support the institution's commitment to growth in molecular pharmacology and in the realm of therapeutic agents to fight chronic diseases such as cancer. This endeavor required broad range of expertise in technology development to establish robust and innovative assays, large collections of diverse chemical and RNAi duplexes to probe specific cellular events, sophisticated compound and data handling capabilities, and a profound knowledge in assay development, hit validation, and characterization. Our goal has been to strive for constant innovation, and we strongly believe in shifting the paradigm from traditional drug discovery towards translational research now, making allowance for unmet clinical needs in patients. Our efforts towards repurposing FDA-approved drugs fructified when digoxin, identified through primary HTS, was administered in the clinic for treatment of stage Vb retinoblastoma. In summary, the overall aim of our facility is to identify novel chemical probes, to study cellular processes relevant to investigator's research interest in chemical biology and functional genomics, and to be instrumental in accelerating the process of drug discovery in academia.

A miniaturized 1536-well format gamma-secretase assay.

gamma-Secretase is an aspartyl protease that cleaves multiple substrates including the amyloid precursor protein (APP) and the Notch proteins. Abnormal proteolysis of APP is involved in the pathogenesis of Alzheimer's disease (AD) and overactive Notch signaling plays an oncogenic role in a variety of cancers. gamma-Secretase has emerged as a promising target for drug development in the treatment of AD and cancer. Assays with increased capacity for high-throughput screening would allow for quicker screening of chemical libraries and facilitate inhibitor development. We have developed a homogeneous time-resolved fluorescence (HTRF)-based assay that makes use of a novel biotinylated recombinant APP substrate and solubilized membrane preparation as the source of the gamma-secretase enzyme. The assay was miniaturized to a 1536-well format and validated in a pilot screen against a library of approximately 3,000 compounds. The overall assay performance was robust due to a calculated Z' factor of 0.74 and its demonstrated ability to identify known gamma-secretase inhibitors such as pepstatin A. This validated assay can readily be used for primary screening against large chemical libraries searching for novel inhibitors of gamma-secretase activity that may represent potential therapeutics for AD and a variety of neoplasms.