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.

Basic cardiovascular risk assessment in naïve patients with colon cancer.

Cardiovascular assessment of oncological patients suggests that cancer can lead to subclinical damage of the heart. The aim of the present study was to analyze the value of baseline cardiovascular biomarkers in patients with newly diagnosed colon cancer prior to treatment. Additionally, another aim was to establish baseline cut-off alert values for this low-intensity neoplastic damage. A total of 51 patients with newly diagnosed colon cancer, without history of cardiac disease, were enrolled in a prospective, cross-sectional study. All patients underwent clinical, biochemical and basic echocardiographic evaluation before starting treatment. Patients were assessed for myocardial damage using high-sensitivity troponin T (hs-TnT), creatine kinase-MB (CK-MB) and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A group of 28 healthy controls was included for comparison. Cardiac ultrasound revealed similar left ventricular (LV) ejection fraction but enlarged LV chambers compared with the control group (LV at end systole, 29.50 vs. 26.00 mm; LV at end diastole, 44.50 vs. 38.00 mm; P<0.001 in both cases). The levels of cardiovascular biomarkers of myocardial damage were higher in the patients than in the control group (CK-MB, 17.00 vs. 11.00 IU/l, P<0.001; hs-TnT, 8.20 vs. 3.00 ng/l, P<0.001; NT-proBNP, 155.40 vs. 48.50 pg/ml, P=0.001). In multivariate analysis, CK-MB and hs-TnT retained statistical significance (P=0.004 and P=0.045, respectively). Moreover, it was demonstrated that new cut-offs for hs-TnT (8.00 ng/l) and NT-proBNP (220.00 pg/ml) can identify cardiac damage in patients ≥65 years old. Thus, the present study confirmed the hypothesis that a basic cardiovascular assessment of treatment-naïve patients with colon cancer can identify important pre-treatment myocardial impact. Adapted cut-off values should be set for cardiovascular biomarkers in the cancer population, different from those currently accepted for acute coronary syndromes or heart failure.

Societal Cost of Ischemic Stroke in Romania: Results from a Retrospective County-Level Study.

BACKGROUND: Health policies in transitioning health systems are rarely informed by the economic burden of disease due to scanty access to data. This study aimed to estimate direct and indirect costs for first-ever acute ischemic stroke (AIS) during the first year for patients residing in Cluj, Romania, and hospitalized in 2019 at the County Emergency Hospital (CEH). METHODS: The study was conducted using a mixed, retrospective costing methodology from a societal perspective to measure the cost of first-ever AIS in the first year after onset. Patient pathways for AIS were reconstructed to aid in mapping inpatient and outpatient cost items. We used anonymized administrative and clinical data at the hospital level and publicly available databases. RESULTS: The average cost per patient in the first year after stroke onset was RON 25,297.83 (EUR 5226.82), out of which 80.87% were direct costs. The total cost in Cluj, Romania in 2019 was RON 17,455,502.7 (EUR 3,606,505.8). CONCLUSIONS: Our costing exercise uncovered shortcomings of stroke management in Romania, particularly related to acute care and neurorehabilitation service provision. Romania spends significantly less on healthcare than other countries (5.5% of GDP vs. 9.8% European Union average), exposing stroke survivors to a disproportionately high risk for preventable and treatable post-stroke disability.

Health-related quality of life in Romanian postmenopausal women with osteoporosis and fragility fractures.

OBJECTIVES: Osteoporosis is a common skeletal disorder characterized by decreased bone mass and increased susceptibility to fractures, which are associated with pain and decrease in physical function, social function, and well-being, which are all aspects of quality of life (QoL). The purpose of this study was to evaluate the burden of osteoporosis and fragility fractures in Romanian postmenopausal women from Cluj County using the 36-Item Short Form Health Survey (SF-36) and Quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) questionnaires. MATERIALS AND METHODS: An analytical cross-sectional study on 364 postmenopausal women was carried out between June 2016 and August 2017 in the Clinical Rehabilitation Hospital in Cluj-Napoca, Cluj County, Romania. Data were collected by interview and from the medical documents: clinical and demographic data, personal medical history, risk factors for osteoporosis, and bone mineral density at the lumbar spine and femur. The patients included in the study were asked to complete the Romanian versions of the SF-36 and QUALEFFO-41 questionnaires. RESULTS: Women with osteoporosis had significantly lower scores in the SF-36 domains (P<0.001) than healthy controls. In the osteoporosis group, a significant association was found in the SF-36 pain domain, where women with a history of fracture had higher scores (P=0.035). As for QUALEFFO-41, a statistical significance was found in the total score (P<0.05), revealing a significantly lower QoL in osteoporotic women with a history of fracture. CONCLUSION: The SF-36 scores registered a loss of QoL in women with osteoporosis. The QUALEFFO-41 total score was significantly lower in the osteoporosis associated with fracture, revealing a lower health-related QoL in these patients.

In vivo assessment of bone marrow toxicity by gold nanoparticle-based bioconjugates in Crl:CD1(ICR) mice.

INTRODUCTION: The present study aimed at evaluating the biodistribution of Tween(®) 20-gold nanoparticle (GNP) conjugates and their potential toxicity on the bone marrow before moving on to Phase I clinical trials. MATERIALS AND METHODS: Tween(®) 20-conjugated GNPs were injected intravenously for 21 days in male Crl:CD1(ICR) mice. Body weight of the mice was evaluated each day. After the sub-chronic Tween(®) 20-GNPs administration, blood samples were harvested, and a full blood count was done individually. Total Au quantity from all major organs was assessed using inductively coupled plasma mass spectrometry. One femur and the sternum obtained from each animal were used for histological assessment. RESULTS: Our data showed that the Tween(®) 20-GNP conjugates were found in large quantities in the bladder. Au was shown to accumulate in the hematopoietic bone tissue, with significant side effects such as leucopoiesis and megakaryopoiesis. The mice had a higher white blood cell and platelet count as opposed to the control group. This suggested that the previously described leukopenic effects of isoflurane were overridden by the leucopoietic effects of Tween(®) 20-GNPs. CONCLUSION: It was uncertain whether the mice were reactive to Au as it is a foreign substance to the tissues or whether the side effects observed were a precursor condition of a more severe hematological condition. Au was found to be hepatotoxic, urging the need for further studies in order to achieve better in vivo compliance and exploit the immense potential of GNPs in cancer pharmacology.

Assessment of a Potential Pharmacokinetic Interaction between Nebivolol and Bupropion in Healthy Volunteers.

BACKGROUND/AIMS: The study aimed at investigating the effects of multiple-dose bupropion (potent inhibitor of CYP2D6) on the pharmacokinetics (PKs) of single-dose nebivolol (CYP2D6 substrate) and to evaluate the clinical relevance of this potential drug interaction. METHODS: This open-label, nonrandomized clinical study had a 2-period design: during period 1 (reference), a single dose of 5 mg nebivolol was administered, while during period 2 (test), 5 mg nebivolol + 300 mg bupropion were ingested concomitantly, after a pretreatment regimen with bupropion (7 days). The PK parameters of nebivolol and its active metabolite were analyzed by noncompartmental modeling, while the pharmacodynamic (PD) parameters (blood pressure and heart rate) were assessed at rest. RESULTS: Bupropion plus nebivolol increased the mean peak plasma concentrations (Cmax) of nebivolol (1.67 ± 0.69 vs. 3.80 ± 1.70 ng/ml) and its active metabolite (0.68 ± 0.22 vs. 1.13 ± 0.38 ng/ml) compared to nebivolol alone. After bupropion pretreatment, the exposure to nebivolol was increased by 7.2-fold for the parent drug and 4-fold for the hydroxylated active metabolite. The difference between the PD parameters measured during the 2 periods was not significant. CONCLUSION: The study concluded that bupropion influenced the PKs of nebivolol in healthy volunteers, but a clinical relevance was not established. However, this latter aspect requires further investigation.