Brain Functional Reserve in the Context of Neuroplasticity after Stroke.

Stroke is the second cause of death and more importantly first cause of disability in people over 40 years of age. Current therapeutic management of ischemic stroke does not provide fully satisfactory outcomes. Stroke management has significantly changed since the time when there were opened modern stroke units with early motor and speech rehabilitation in hospitals. In recent decades, researchers searched for biomarkers of ischemic stroke and neuroplasticity in order to determine effective diagnostics, prognostic assessment, and therapy. Complex background of events following ischemic episode hinders successful design of effective therapeutic strategies. So far, studies have proven that regeneration after stroke and recovery of lost functions may be assigned to neuronal plasticity understood as ability of brain to reorganize and rebuild as an effect of changed environmental conditions. As many neuronal processes influencing neuroplasticity depend on expression of particular genes and genetic diversity possibly influencing its effectiveness, knowledge on their mechanisms is necessary to understand this process. Epigenetic mechanisms occurring after stroke was briefly discussed in this paper including several mechanisms such as synaptic plasticity; neuro-, glio-, and angiogenesis processes; and growth of axon.

AOTMiT reimbursement recommendations compared to other HTA agencies.

Our objective was to compare AOTMiT (Polish: Agencja Oceny Technologii Medycznych i Taryfikacji) recommendations to other HTA (Health Technology Assessment) agencies for newly registered drugs and new registration indications issued by the European Medicines Agency between 2014 and 2019. The study aims to assess the consistency and justifications of AOTMiT recommendations compared to that of other HTA agencies in 11 countries. A total of 2494 reimbursement recommendations published by 12 HTA agencies for 464 medicinal products and 525 indications were analyzed. Our analysis confirmed that the Polish AOTMiT agency seems to bear the closest resemblance to the corresponding HTA agencies from Canada (CADTH) and New Zealand (PHARMAC), when it comes to the outcome of HTA recommendations (positive or negative). Poland had a general scheme for justifying recommendations, similar to that of Ireland-four aspects (i.e., clinical efficacy, safety profile, cost-effectiveness, and impact on the payer's budget) are important for Poland when formulating the final decision. Compared to other countries, Poland shows a noticeably different pattern of justifying reimbursement recommendations, as revealed primarily in terms of budget impact and somewhat less so for cost-effectiveness rationales.

Reimbursement decision-making system in Poland systematically compared to other countries.

Introduction: Our objective was to analyze and compare systematically and structurally reimbursement systems in Poland and other countries. Methods: The systems were selected based on recommendations issued by the Polish Agency for Health Technology Assessment and Tariffication (AHTAPol), which explicitly referred to other countries and agencies). Consequently, apart from Poland, the countries included in the analysis were England, Scotland, Wales, Ireland, France, Netherlands, Germany, Norway, Sweden, Canada, Australia and New Zealand. Relevant information and data were collected through a systematic search of PubMed (Medline), Embase and The Cochrane Library as well as competent authority websites and grey literature sources. Results and discussion: In most of the countries, the submission of a reimbursement application is initiated by a pharmaceutical company, and only a few countries allow it before a product is approved for marketing. All of the agencies analyzed are independent and some have regulatory function of reimbursement decision making body. A key criterion differentiating the various agencies in terms of HTA is the cost-effectiveness threshold. Most of the countries have specific mechanisms to improve access to expensive specialty drugs, including cancer drugs and those used for rare diseases. Reimbursement systems often lack consistency in appreciating the same stages, leading to heterogeneous decision-making processes. The analysis of recommendations issued in different countries for the same medicinal product will allow a better understanding of the relations between the reimbursement system, HTA assessment, stakeholders involvement and decision on reimbursement of innovative drugs.

The impact of changing the funding model for genetic diagnostics and improved access to personalized medicine in oncology.

AIM: In January 2017, a new funding model for diagnostic genetic testing in cancer was introduced in Poland. OBJECTIVES: The aim of this study was to assess the impact of changing the funding model for genetic diagnosis in oncology on improving access to personalized medicine in Poland between 2017 and 2019. METHODS: The analysis included data on settlements with the National Health Fund for genetic tests in cancer under a contract of the hospital treatment type and under the contract in the type of separately contracted services between 2017 and 2019. RESULTS: The 150,647 diagnostic genetic tests were reported, which were billed to 111,872 patients. The average number of tests per patient was 1.35. One test was billed to 83.5% of patients, 11.2% of patients had two tests billed, and 5.3% had at least three tests billed. The number of services provided under the hospital treatment contract in 2018 doubled compared to the previous year. For separately contracted services, more than threefold increase in genetic testing performed in 2019 compared to 2018 was observed. CONCLUSION: our data show that the novel funding model for genetic services introduced in Poland has positive impact on the availability of genetic testing for patients.

Strontium Ranelate and Strontium Chloride Supplementation Influence on Bone Microarchitecture and Bone Turnover Markers-A Preliminary Study.

Despite strontium ranelate use in osteoporosis management being one of the promising concepts in disease treatment, there is no clear evidence that strontium organic compounds are more effective than inorganic ones. The aim of this study was to compare strontium chlorate and strontium ranelate influence on the mice bone microarchitecture. We investigated whether strontium chlorate (7.532 mmol/L) and strontium ranelate (7.78 mmol/L) solutions fed to healthy SWISS growing mice (n = 42) had an influence on the percent of bone volume (BV/TV), trabecular thickness (Tb.Th), number of trabeculae (Tb.N), and separation between each trabecula (Tb.Sp) in the chosen ROI (region of interest) in the distal metaphysis of the left femurs. The cortical bone surface was examined close to the ROI proximal scan. There was an increase in each examined parameter compared with the control group. There were no statistical differences between strontium ranelate and strontium chlorate parameters. Our study indicates that organic and inorganic strontium compounds similarly affect the bone microarchitecture and strength.

Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-naïve metastatic clear-cell renal cell carcinoma-A network meta-analysis. Focus on cabozantinib combined with nivolumab.

Introduction: The combination of immunotherapy and targeted therapy is currently marking a new era in the treatment of renal cancer. The latest clinical guidelines recommend the use of drug combinations for the first-line treatment of advanced renal cancer. The aim of this review is to compare the efficacy of combined cabozantinib + nivolumab therapy with other immune checkpoint inhibitors combined with tyrosine kinase inhibitors or monoclonal antibodies blocking the CTLA-4 (cytotoxic T cell antigen 4) in the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC). Methodology: A systematic literature search was carried out in the PubMed and EMBASE databases. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-naïve metastatic RCC (i.e., lenvatinib + pembrolizumab, axitinib + pembrolizumab and nivolumab + ipilimumab) were searched. A network meta-analysis (NMA) was performed for data synthesis. The methodology of included RCTs was assessed using the Cochrane RoB two tool. The data were analyzed in the overall population as well as in risk subgroups defined according to the International Metastatic Database Consortium (IMDC) i.e., patients with a favorable and intermediate or poor prognoses. The most recent cut-off dates from included studies were analyzed. Results: Four RCTs (CheckMate 9 ER, KEYNOTE-426, CLEAR and CheckMate 214) were included in the review. No studies directly comparing cabozantinib + nivolumab with any of the drug combinations included in this review were available. NMA showed that cabozantinib + nivolumab was superior compared to axitinib + pembrolizumab and nivolumab + ipilimumab in all analyzed comparisons (overall population and IMDC risk subgroups), both in terms of overall survival and progression-free survival (PFS). The advantage of cabozantinib + nivolumab was statistically significant only for PFS when compared to nivolumab + ipilimumab in the overall population. The results for the comparison of cabozantinib + nivolumab with lenvatinib + pembrolizumab showed numerical superiority of lenvatinib + pembrolizumab combination in terms of overall survival, but none of the results were statistically significant. The advantage of lenvatinib + pembrolizumab over cabozantinib + nivolumab in terms of PFS was statistically significant in the overall and favorable prognosis population. Conclusion: Inclusion of the most recent cut-off data from CheckMate 9 ER did not affect the role of the cabozantinib + nivolumab combination for treatment-naïve metastatic RCC. Cabozantinib + nivolumab is an effective therapeutic option for the first-line treatment of advanced renal cancer that is recommended both in the latest European and American guidelines for all IMDC risk groups.

Recommendations for the Implementation of Hospital Based HTA in Poland: Lessons Learned From International Experience.

Introduction: The main challenge of modern hospitals is purchasing medical technologies. Hospital-based health technology assessments (HB-HTAs) are used in healthcare facilities around the world to support management boards in providing relevant technologies for patients. Aim: This study was undertaken to update the existing body of knowledge on the characteristics of HB-HTA systems/models in the selected European countries. Insights gained from this study were used to provide an optimal approach for implementing HB-HTA in Poland. Materials and methods: Firstly, we carried out a systematic review in PubMed and embase. Secondly, we searched for gray literature via the AdHopHTA online handbook and the design book of the AdHopHTA project, as well as literature describing healthcare systems provided by the WHO. Then, we conducted in-depth interviews with HB-HTA experts from four countries. Finally, we selected ten countries from Europe and prepared frameworks for data collection and analyses. Results: The selected countries (Switzerland, Spain, France, Italy, Denmark, Finland, Sweden, the Netherlands, and Austria) are examples of decentralized or deconcentrated healthcare systems. In terms of HB-HTA, differences in organisational models (independent group, stand-alone, integrated-essential, integrated-specialised), type of financing (internally vs. externally), collaboration with an HTA National Agency and other stakeholders (e.g., Patients' Associations) were identified. HB-HTA engages multi-skilled staff with various academic backgrounds and operates mainly on a voluntary basis. Conclusion: Strengths and weaknesses associated with various organisational models must be carefully considered in the context of support for decentralized or centralized models of implementation while embarking on HTA activities in Polish hospitals.

Economic Costs of Cardiovascular Diseases in Poland Estimates for 2015-2017 Years.

BACKGROUND: Cardiovascular diseases are associated with growing public and private expenditure on healthcare regardless geographic region. Therefore, it is necessary to accurately estimate the overall societal costs-both direct and indirect expenses from the perspective of patients, caregivers and employers. RESEARCH DESIGN: The aim of this paper is to determine the direct and indirect costs related to cardiovascular diseases in Poland from 2015 to 2017. All costs are estimated based on data available in the public domain and obtained from the major Polish institutions. Indirect costs were calculated using a modified human capital approach. RESULTS: The financial burden of cardiovascular diseases in Poland is significant. This study revealed that total costs (direct and indirect) of cardiovascular diseases, for 2015-2017, range from 34.9 bn PLN (8.2 bn EUR) to over 40.9 bn PLN (9.6 bn EUR). Total direct cost and indirect costs were approximately 6.1 bn PLN (1.4 bn EUR) (16%) and 31.3 bn PLN (7.3 bn EUR) (84%), respectively. CONCLUSION: Collectively, the estimated direct and indirect cost of cardiovascular diseases provide a useful input for economic impact assessments of public health programs and health technology analyses.

Prevalence and selected determinants of the risk of problem gambling among Polish secondary school students.

OBJECTIVE: The study had two aims. The first was to determine the prevalence of various types of gambling behaviour and the severity of gambling among secondary school students in one of the poorest provinces in Poland. The second was to identify correlations between selected socio-demographic variables and the severity of gambling problems. MATERIAL AND METHODS: The study was carried out on a group of teenagers from secondary schools in the Lublin Province of eastern Poland. The survey covered 923 respondents aged 17 - 21 (M=18.06; SD=0.367). The study used a list of gambling activities, the South Oaks Gambling Screen-Revised Adolescent (SOGS-RA), and a socio-demographic questionnaire. The effects of independent variables on the severity of gambling behaviour were evaluated using the Mann-Whitney U test (for binary variables, such as gender or age group) and Kruskal-Wallis one-way ANOVA for ternary variables (e.g., place of residence, type of school). RESULTS AND CONCLUSIONS: The findings show that in the studied population 7.2% were pathological gamblers and 41.8% had not gambled during the 12 months prior to the study. These findings are consistent with the literature. There seems to be a clear trend in which pathological gambling is found most frequently among technical secondary school students, and least frequently among those from secondary schools of general education. In addition, persons who had lived (until the age of 10) in rural areas scored the lowest in SOGS-RA, while those from cities below 50,000 residents, scored the highest. In families with a gambling member, pathological gambling was found 1.7 times more frequently.

Overview and Analysis of the Cost of Drug Programs in Poland: Public Payer Expenditures and Coverage of Cancer and Non-Neoplastic Diseases Related Drug Therapies from 2015-2018 Years.

BACKGROUND: In Poland drug programmes developed by the Minister of Health and financed by the National Health Fund are special reimbursement frameworks of innovative, expensive, and mostly hospital based medical products used for a small number of patients. RESEARCH DESIGN: The research presented in this paper is based on data analysis published by the National Health Fund in Poland. The analysis focused on estimating public payer expenditure on drugs available within drug programmes from 2015 to 2018. RESULTS: In subsequent years, reimbursement of drugs used within drug programmes was associated with the National Health Fund budget expenditure of 635 mln USD, 755 mln USD, 854 mln USD, and 921 mln USD, respectively. Reimbursement of oncology drug programmes constituted 48.1%, 42.5%, 47.1%, and 52.4% and were approximately 305, 312, 402, 483 mln USD, whereas values of non-oncology drug programmes were approximately 330, 434, 452, and 438 mln USD which constituted 51.9%, 57.5%, 52.9%, and 47.6% respectively. CONCLUSION: Despite the fact that the expenditure on drug programs in Poland are increasing every year, they undoubtedly improve the patient's access to the most innovative oncological and nononcological therapies in the Polish healthcare system.

The direct and indirect costs of epilepsy in Poland estimates for 2014-2016 years.

BACKGROUND: According to the current data, around 1% of the Poland population have epilepsy, which comprises about 400,000 people. This group of patients requires life-long therapy including both drug therapy and hospitalization. The character of the epilepsy has a significant impact on the expenses borne by individual patients, and the prevalence of the disease has a significant impact on the health care system. METHODS: This article aims to measure the direct and indirect costs of epilepsy in Poland estimates for the years 2014-2016 (top-down approach). We use a modified human capital approach and a unique dataset provided by the number of Polish institutions including National Health Fund, Social Insurance Institution, and Central Statistical Office. RESULTS: Epilepsy burden in Poland is significant. In the years 2014-2016, the total direct cost of epilepsy amounted to, respectively, 355 mln PLN (84 mln EUR), 368 mln PLN (87 mln EUR), and 373 mln PLN (88 mln EUR), but the total indirect cost amounted to 1 bn PLN (239 mln EUR), 949 mln PLN (224 mln EUR), and 848 mln PLN (200 mln EUR). CONCLUSIONS: Direct and indirect costs of epilepsy can be a useful input for health technology analyses of drugs or economic impact assessments of public health programs.

[Cytostatic and cytotoxic waste - rules of conduct in Poland]. / Odpady cytostatyczne i cytotoksyczne ­ zasady postepowania w Polsce.

Poland is one of the European countries with the highest level of production of dangerous medical waste. Although in Europe the volume of produced cytotoxic and cytostatic waste (used in chemotherapy by oncological patients) has been declining for several years, in Poland a reverse trend has been observed. As this waste puts the safety of medical workers and patients at risk, special handling procedures are required to limit the harmful effect of these drugs on human health. In view of the above, the aim of the work was to present the rules of conduct with cytotoxic and cytostatic drugs, and their waste, in Poland. Med Pr. 2019;70(3):377-91.

Indirect costs of diabetes and its impact on the public finance: the case of Poland.

BACKGROUND: Growing public and private expenditure on healthcare results i.a. from the spreading of chronic diseases. Diabetes belongs to the most frequent ones, beyond neoplasms and cardiological diseases, and hence generates a significant burden for the public finance in terms of the direct costs. However, the economy suffers also from the indirect cost of diabetes that manifests itself in the loss in Gross Domestic Product (GDP) and general government revenues. METHODS: This paper aims to measure this indirect cost, both in terms of GDP drop (social perspective) and public revenue drop (public finance perspective), in the case of Poland in 2012-2014. We use a modified human capital approach and unique dataset provided by the Social Security institution in Poland and the Polish Central Statistical Office. RESULTS: Diabetes is a substantial and growing burden for the Polish economy. In the years 2012, 2013 and 2014 the indirect cost (output loss) amounted to 1.85 bn USD, 1.94 bn USD and 2.00 bn USD respectively. CONCLUSIONS: Estimated indirect cost of diabetes can be a useful input for health technology analyses of drugs or economic impact assessments of public health programmes.