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.

Clinical Utility of Boston-CTS and Six-Item CTS Questionnaires in Carpal Tunnel Syndrome Associated with Diabetic Polyneuropathy.

Diabetic polyneuropathy (DPN) is the most frequent complication of diabetes. Carpal tunnel syndrome (CTS), one of the most common neuropathies, is a chronic compression of the median nerve at the wrist. In our prospective cross-sectional study, we enrolled patients with type 2 diabetes presenting with signs and symptoms suggestive of DPN (n = 53). We aimed to compare two clinical scales: the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) and the six-item CTS symptoms scale (CTS-6), with nerve conduction studies (NCS) for detecting CTS in patients with DPN. Carpal tunnel syndrome and DPN were clinically evaluated, and the diagnosis was confirmed by NCS. Depending on the NCS parameters, the study group was divided into patients with and without DPN. For each group, we selected patients with CTS confirmed through NCS, and the results were compared with the BCTQ and CTS-6 scales. The clinical evaluation of CTS performed through BCTQ and CTS-6 was statistically significantly different between patients with and without CTS. When comparing the BCTQ questionnaire with the NCS tests, we found area under the curve (AUC) = 0.76 (95% CI 0.65-0.86) in patients with neuropathy and AUC = 0.72 (95% CI 0.55-0.88) in patients without neuropathy. At the same time, the AUC values of the CTS-6 scale were 0.76 (95% CI 0.61-0.88) in patients with neuropathy and 0.70 (95% CI 0.51-0.86) in patients without neuropathy. Using multiple logistic regression, we demonstrated that DPN increased the chances of detecting CTS using the two questionnaires. The Boston Carpal Tunnel Syndrome and CTS-6 questionnaires can be used in the diagnosis of CTS in diabetic patients with and without DPN but with moderate AUC. The presence of DPN increased the chances of detecting CTS using the BCTQ questionnaire and the CTS-6 scale.

The Effect of Cerebrolysin on the Predictive Value of Baseline Prognostic Risk Score in Moderate and Severe Traumatic Brain Injury.

Cognitive dysfunction is a significant complaint among patients after moderate to severe traumatic brain injury (TBI), with devastating consequences on functional recovery and quality of life. Prognostic models allow a better assessment and management of neurotrauma patients. The aim of the study was to demonstrate the predictive value of the Baseline Prognostic Risk Score (BPRS) in moderate to severe TBI, in a sample of patients treated with neurotrophic factors. Eighty patients with moderate-severe TBI from the CAPTAIN II study were included in secondary data analysis. Patients received active treatment with Cerebrolysin, 50 mL per day for ten days, followed by two treatment cycles with 10 mL per day for ten days. BPRS was determined on admission; the age was recorded, and patients were evaluated using the following neurocognitive tests: Mini-Mental State Essay (MMSE), Wechsler Adult Intelligence Scale-Third Edition Processing Speed Index (WAIS-III PSI) and Stroop Colour Word Test-Victoria Version at 10, 30 and 90 days. Hierarchical regression analysis was performed to investigate the unique predictive value of BPRS on cognitive evolution, independent of age. BPRS independently predicted scores on the WAIS-III PSI DSCales and the Word subscale of the Stroop Colour Word Test at 90 days. Age was a significant predictor for all the investigated scales at 10, 30, and 90 days. This study demonstrates the predictive value of a validated prognostic model (BPRS) for medium-term neurocognitive outcomes in a sample of moderate-severe traumatic brain injury treated with neurotrophic factors.

Superior neuroprotective effects of cerebrolysin in heat stroke following chronic intoxication of Cu or Ag engineered nanoparticles. A comparative study with other neuroprotective agents using biochemical and morphological approaches in the rat.

The possibility that cerebrolysin, a mixture of several active fragments of neurotrophic factors and peptides induces neuroprotection following nanoparticles induced exacerbation of brain damage in heat stroke was examined in a rat model. For this purpose, the therapeutic efficacy of Cerebrolysin (2.5 or 5 ml/kg) recommended for stroke treatment was used in comparison with other drugs in standard doses recommended for such therapy in clinical situations e.g., levetiracetam (44 mg/kg), pregabalin (200 mg/kg), topiramate (40 mg/kg,i.p.) and valproate (400 mg/kg). Rats subjected to 4 h heat stress in a biological oxygen demand (BOD) incubator at 38 degrees C (Rel Humid 45-47%; Wind vel 22.4 to 25.6 cm/sec) developed profound behavioral symptoms of heat stroke e.g., hyperthermia, profuse salivation, prostration and gastric ulcerations in the stomach. These rats also exhibited marked brain pathology at this time. Thus, breakdown of the blood-brain barrier (BBB) to proteins associated with brain edema formation could be seen in these heat stressed rats as compared to control groups. The edematous brain areas showed profound neuronal damage and/or distortion in large areas of the neuropil. These pathological symptoms were further exacerbated in Cu or Ag nanoparticles treated group (50-60 nm particle size, 50 mg/kg, i.p./day for 7 days) after identical heat stress on the 8th day. Pretreatment with cerebrolysin (2.5 ml/kg, i.v.) daily for 3 days in normal rats before heat stress significantly reduced the behavioral stress symptoms and the breakdown of the BBB function, edema formation and neuronal injuries. However, the magnitude and intensity of these neuroprotective effects were much less intense in all other drug treated rats after similar heat stress. On the other hand, almost double dose of cerebrolysin (5 ml/kg) was needed to achieve comparable neuroprotection in nanoparticles treated animals after heat stress. Whereas, double dose of all other compounds was much less effective in inducing neuroprotection in nanoparticles treated heat-exposed animals. These observations are the first to show that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal and in nanoparticles treated group. Furthermore, cerebrolysin in double dose was the most effective in inducing neuroprotection in nanoparticles treated heat exposed rats on brain pathology as compared to double doses of other drugs. Taken together, our results show that cerebrolysin has the most superior neuroprotective effects on brain pathology in heat stroke in both normal and nanoparticles treated rats as compared to other contemporary neuroprotective agents, not reported earlier.