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.

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

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.

Two years of the COVID-19 pandemic from a child's perspective: A narrative review.

The coronavirus disease 2019 (COVID-19) pandemic has been ongoing since 2020. This period is characterized by a significant change in people's lifestyles. Children are a particularly affected group. In order to determine the impact of the pandemic on children's lives, scientific publications available in PubMed, Google Scholar, and The United Nations Children's Fund (UNICEF) Innocenti's Children and COVID-19 Library were reviewed, and the statistical data made available by the Polish Ministry of Health on incidence, death and vaccination rates was analyzed. Even if children were not infected with the virus, they felt the effects of the pandemic through restrictions in the daily functioning of schools, service facilities and households. Despite the relatively mild symptoms accompanying infections in pediatric patients, as well as the low rates of hospitalization and mortality, the pandemic have had numerous negative effects on children's mental and physical health that may trigger further "non-communicable epidemics". Weight changes, limitations in physical activity, and the intensification of social and emotional problems will certainly have a negative impact on their future lives. The introduction of vaccination for children over the age of 5 brought hope, but since then, it has been accompanied by controversy and uncertainty. Further research is necessary to determine the impact of the COVID-19 pandemic on children.

Colorectal Cancer-The Worst Enemy Is the One We Do Not Know.

BACKGROUND: Colorectal cancer is one of the most common cancers in humans. It is the third most frequently diagnosed malignant neoplasm and is the second highest cause of cancer mortality in the world. Every year, more and more people die of colorectal cancer because the diagnosis is conducted too late. This shows how important a role screening tests and the awareness of the population about the symptoms play in this aspect. This article aimed to determine the knowledge of the Polish population about morbidity, symptoms, prevention, and subjective feelings about the level of availability of knowledge about colorectal cancer. METHODS: In 2020, a study was conducted using an online questionnaire assessing the awareness of the Polish population about colorectal cancer. A self-authored questionnaire including questions about socio-demographic characteristics, and 18 questions related to substantive issues, was used. A research group was selected (n = 633). The substantive part of the questionnaire included questions examining the respondents' knowledge about morbidity, symptoms, prevention, and subjective feelings about the level of availability of knowledge about colorectal cancer. RESULTS: The respondents' awareness level was influenced by demographic factors, such as gender: (p < 0.05) and age (p < 0.05) and social factors, such as: level of education (p < 0.05) or professional situation (p < 0.05). Compared to thematic articles from other countries, the research group was divided into smaller subgroups due to the abovementioned factors, due to which it was possible to stratify and analyze the significance of differences between them.

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.

Biomarkers and Genetic Markers of Hepatocellular Carcinoma and Cholangiocarcinoma-What Do We Already Know.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with an increasing worldwide mortality rate. Cholangiocarcinoma (CCA) is the second most common primary liver cancer. In both types of cancers, early detection is very important. Biomarkers are a relevant part of diagnosis, enabling non-invasive detection and control of cancer recurrence, as well as in the application of screening tests in high-risk groups. Furthermore, some of these biomarkers are useful in controlling therapy and treatment selection. Detection of some markers presents higher sensitivity and specificity in combination with other markers when compared with a single detection. Some gene aberrations are also prognostic markers in the two types of cancers. In the following review, we discuss the most common biomarkers and genetic markers currently being used in the diagnosis of hepatocellular carcinoma and cholangiocarcinoma.

A Systematic Review of the Cyclooxygenase-2 (COX-2) Expression in Rectal Cancer Patients Treated with Preoperative Radiotherapy or Radiochemotherapy.

The main objective of this systematic review is to investigate the expression level of the cyclooxygenase-2 (COX-2) in rectal cancer treated with either preoperative radiotherapy or radiochemotherapy. In addition, we have summarized the effects of preoperative treatment of rectal cancer with regards to the expression levels of COX-2. A systematic literature review was performed in The Cochrane Library, PubMed, Web of Science, and Scopus databases on 1 January 2021 with the usage of the following search string-(cyclooxygenase-2) OR (COX-2) AND (rectal cancer) AND (preoperative radiochemotherapy) OR (preoperative radiotherapy). Among the 176 included in the analysis, only 13 studies were included for data extraction with a total number of 2095 patients. The results of the analysis are based on the articles concerning the expression of COX-2 in rectal cancer among patients treated with preoperative radiotherapy or radiochemotherapy. A COX-2 expression is an early event involved in rectal cancer development. In cases of negative COX-2 expression, radiotherapy and radiochemotherapy might contribute to the reduction of a local recurrence. Therefore, COX-2 may be considered as a biologic factor while selecting patients for more effective, less time-consuming and less expensive preoperative treatment. However, the utility of the administration of COX-2 inhibitors to patients with COX-2 overexpression, in an attempt to improve the patients' response rate to the neoadjuvant treatment, needs an assessment in further clinical trials.

Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients.

BACKGROUND: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod. METHODS: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated. RESULTS: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy. CONCLUSION: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.

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.

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.

Decreased Cerebrospinal Fluid Orexin-A (Hypocretin-1) Concentrations in Patients after Generalized Convulsive Status Epilepticus.

The effects of status epilepticus on the orexin/hypocretin system have yet to be investigated. The present study aimed to assay orexin-A/hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized convulsive status epilepticus (GCSE). The study groups included 20 GCSE patients, 24 patients diagnosed with epilepsy but remaining in remission (ER), and 25 normal controls (CTR). Diagnostic lumbar puncture was performed in GCSE patients within 3-10 days of seizure cessation, as well as in the ER and to CTR subjects. Among all GCSE patients, the outcome was graded according to the modified Rankin Scale (mRS) at 1-month follow-up. Orexin-A levels were measured in unextracted CSF samples, using a commercial radioimmunoassay. There was a significant overall difference in median CSF orexin-A concentrations between GCSE, RE, and CTR patients (p < 0.001). The lowest concentrations were noted in the GCSE group compared to ER (p < 0.001) or CTR (p < 0.001). CSF orexin-A levels in GCSE patients inversely correlated with clinical outcome as assessed on the mRS at 1-month follow-up (r = -0.55; p = 0.1). In conclusion, CSF orexin-A levels may serve as a biomarker of increased turn-over of the peptide or post-SE neuronal damage, and implicates the orexin system in the pathogenesis of SE.

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.

Robotic assistance for people with dementia: a viable option for the future?

INTRODUCTION: Demographic changes in society and fewer personnel working in healthcare services have resulted in an increase in the speed of development of safe, reliable robotic assistance technologies for patients with neurological diseases. This paper aims to advocate for the frailty of patients in light of the economic need for robotic assistance, discuss potential hazards, and outline related factors that influence positive outcomes. AREAS COVERED: This article reviews the state of the art and perspectives regarding the use of robotics in older adults with dementia. We focus on current trends in the development of robotic technologies for these patients and discuss the potential hazards associated with the implementation of such cutting-edge technology in daily practice. EXPERT OPINION: We envisage a gradual increase in the usage of robot-based devices for the management and support of patients with cognitive deficits. In particular, the introduction of artificial intelligence will enhance the functionality of these technologies, but also increase potential hazards resulting from human-robot interactions. The development of such technology must consider whether neurological syndromes are static or progressive. Progressive syndromes pose the biggest challenge since the functionality of robotic devices must adapt to patients changing cognitive and motor performance profiles.

[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.

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.