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The paper focuses on knowledge generation, a topic frequently overlooked in the traditional debates in epistemology and philosophy of science. We focus on investigation as the primary process generating knowledge and its products. Investigation is taken as a generalization of the research process that includes similar knowledge-generating practices in aboriginal communities. To characterize the complexity of investigation processes and their products we go beyond traditional epistemological characterization of knowledge in terms of mental states and turn to the concept of routine. Investigation processes share a common symbolic representation form which we call here a knowledge thread. The dynamics of the knowledge thread may be characterized by two intertwined tiers: cognitive and institutional. Using examples from our previous studies, especially on the recent discovery of microRNAs in molecular biology, we illustrate the dynamics of threads and claim that it is susceptible to the social network analysis which, however, requires insightful applications and sound interpretation of the results. Such an interpretation, as we suggest, may further be elaborated on the grounds of anthropological theories of distributed agency and distributed cognition.

Background: The recent development of new antileukemic therapies (anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhbitors, phosphoinositide 3-kinase inhibitors, and B-cell lymyphoma-2 antagonists) improved the progression-free survival (PFS) compared with selected standard regimens in clinical trials for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Unfortunately, the relative efficacy of all possible therapeutic options remains unknown because there is no direct evidence for all possible comparisons. Objectives: We aimed to compare the efficacy and safety of novel agents, chemotherapy, and immunotherapy using a Bayesian network meta-analysis (NMA). Design: Systematic literature review with Bayesian NMA. Methods: An extensive systematic literature review of randomized clinical trials for relapsed/refractory CLL was performed. We searched for articles indexed in medical databases (MEDLINE, Embase, The Cochrane Library) and gray literature that could be further implemented into the Bayesian NMA. Results: The systematic search identified 15 randomized trials that formed networks comparing PFS, overall survival (OS), overall response rates, and serious adverse events. Our study showed that all regimens containing novel agents significantly prolonged PFS compared with standard chemoimmunotherapy and immunotherapy. Among targeted drugs, venetoclax (VEN) + rituximab (RTX) had comparable efficacy in terms of PFS to zanubrutinib (ZAN) [hazard ratio (95% credible interval), 1.10 (0.59–2.08)], acalabrutinib (ACA) [0.78 (0.47–1.30)], ibrutinib (IBR) monotherapy [0.72 (0.41–1.27)], and other IBR-based regimens. ZAN was superior to IBR monotherapy [0.65 (0.49–0.86)] but not to ACA [0.71 (0.49–1.02)]. There were no significant differences in OS in any of the above comparisons. Conclusion: All novel therapies have better efficacy than chemoimmunotherapy and immunotherapy regimens. Among novel agents, the relative efficacy of VEN + RTX was similar to all BTKi, while ZAN was superior to IBR and comparable to ACA. Trial registration: PROSPERO CRD42022304330. [ABSTRACT FROM AUTHOR]

The aim of this paper is to examine a complex pattern of mutual interdependence between Unified Growth Theory (subroutine) and the evolution of the entire field of economic growth theories (main routine) from a philosophical and methodological perspective. The analysis utilises the recently introduced concept of research routine (and respectively, subroutine) aimed at an explanation of the evolution of scientific research. The study identifies the influence of the subroutine (and its specific concept of demographic transition) on the core concepts of the main routine: human capital, population growth and learning. The results are based on network analyses of extensive bibliometric evidence from Scopus and the Web of Knowledge.

Of the three main areas of science studies that emerged after WWII (Kawalec, 2018), namely social studies of science, economics of knowledge and scientometrics, it was the latter that gained particular prominence in science policy around the 1990’s with the advent of New Public Management (Pollitt, Thiel, & Homburg, 2007). One of its focal areas has been identification of emerging topics in science. They are incessantly assumed to be an outcome of a simple cumulative progress of scientific knowledge (Price, 1976; Merton, 1988; Bird, 2007; Fochler, 2016). In my paper I challenge this assumption of simple cumulativity and argue that the emergence of breakthrough topics in science is preceded by a sequence of transformation phases. Using the example of “microRNA&cancer” as an emergent topic identified by a quantitative analysis of a large dataset of publications (Small et al. 2014) I demonstrate that the proposed analysis of transformation phases complements big data quantitative analyses with theoretical understanding of the dynamics mechanism and, in effect, leads to a more adequate characterization of the topic itself as well as a more precise identification of the source publications. While the proposed method uses a more complex (meso-level) unit of analysis (i.e. “research routines”) instead of citations and co-occurrence of single publications (micro-level), it integrates quantitative with qualitative analyses.

Background. Knowledge of dietary patterns is crucial for dietary behaviours interventions. Objectives. The aim of the study was to describe the dietary patterns of children between the ages of 6-10 years from primary schools in Lesser Poland. Material and methods. The study was carried out between 2008-2012 and included 1,140 children and their parents. The questionnaire for parents included socio-economic questions about the family, parents' education and frequency of consuming selected food products by children. The Food Frequency Questionnaire covered 21 selected food groups, and fast food and snacking were also asked about. Based on anthropometric measurements, the body mass index (BMI) was calculated for each child. Factor analysis and cluster analysis were used to identify individual dietary patterns of children. Results. Three cluster groups were distinguished showing the eating patterns of the children. Children from cluster 1 (healthy) showed the most health-promoting model of nutrition. They often consumed butter, vegetable oils, groats, pasta and rice, wholemeal bread, fish and fish products, red meat, eggs, raw vegetables, cooked vegetables, pulses, unsalted nuts and yellow cheese. The cluster representing the mixed feeding model (2) least frequently consumed salty snacks. Children from cluster 3 (unhealthy) more often consumed chips, crisps and salty sticks than cluster 2 and were more often overweight and obese than children from cluster 1. The education level and average monthly income were significantly higher in the families of children from the healthy cluster compared with those from the unhealthy cluster. Conclusions. Dietary patterns in children are influenced by socio-economic and parental education factors. Overweight and obese children presented unhealthy nutrition behaviours. [ABSTRACT FROM AUTHOR]

Major depressive disorder is one of the most severe mental disorders. It strongly impairs daily functioning, and, in extreme cases, it can lead to suicide. Although different treatment options are available for patients with depression, there is an ongoing search for novel therapeutic agents, such as scopolamine (also known as hyoscine), that would offer higher efficacy, a more rapid onset of action, and a more favorable safety profile. The aim of our study was to review the current clinical evidence regarding the use of scopolamine, a promising therapeutic option in the treatment of depression. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases up to 5 June 2023. We included randomized placebo-controlled or head-to-head clinical trials that compared the clinical efficacy and safety of scopolamine in the treatment of major depressive disorder. Two reviewers independently conducted the search and study selection and rated the risk of bias for each study. Four randomized controlled trials were identified in the systematic review. The included studies investigated the use of scopolamine administered as an oral, intramuscular, or intravenous drug, alone or in combination with other antidepressants. The results indicated that scopolamine exerts antidepressant effects of varying intensity. We show that not all studies confirmed a statistically and clinically significant reduction of depressive symptoms vs. placebo. A broader perspective on scopolamine use in antidepressant treatment should be confirmed in subsequent large randomized controlled trials assessing both effectiveness and safety. Therefore, studies directly comparing the effectiveness of scopolamine depending on the route of administration are required. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the safety profile of tyrosine kinase inhibitors (TKIs) approved for use as monotherapy or combination therapy for the first-line treatment of adult patients with metastatic clear cell renal cell carcinoma (RCC). Methods: A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials (RCTs) investigating the use of: cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib, cabozantinib + nivolumab, lenvatinib + pembrolizumab, axitinib + avelumab, and axitinib + pembrolizumab in previously untreated adult patients with metastatic clear cell RCC. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The risk of bias for RCTs was assessed using the Cochrane Collaboration tool. The P score was used to determine the treatment ranking. The mean probability of an event along with the relative measures of the NMA was considered with the treatment rankings. Results: A total of 13 RCTs were included in the systematic review and NMA. Sorafenib and tivozanib used as monotherapy were the best treatment options. Sorafenib achieved the highest P score for treatment discontinuation due to adverse events (AEs), fatigue, nausea, vomiting of any grade, and hypertension of any grade or grade ≥3. Tivozanib achieved the highest P score for AEs, grade ≥3 AEs, dose modifications due to AEs, and grade ≥3 diarrhea. Sunitinib was the best treatment option in terms of diarrhea and dysphonia of any grade, while cabozantinib, pazopanib, and axitinib + pembrolizumab-in terms of grade ≥3 fatigue, nausea, and vomiting. TKIs used in combination were shown to have a poorer safety profile than those used as monotherapy. Lenvatinib + pembrolizumab was considered the worst option in terms of any AEs, grade ≥3 AEs, treatment discontinuation due to AEs, dose modifications due to AEs, fatigue of any grade, nausea, vomiting, and grade ≥3 nausea. Axitinib + avelumab was the worst treatment option in terms of dysphonia, grade ≥3 diarrhea, and hypertension, while cabozantinib + nivolumab was the worst option in terms of grade ≥3 vomiting. Interestingly, among the other safety endpoints, cabozantinib monotherapy had the lowest P score for diarrhea and hypertension of any grade. Conclusion: The general safety profile, including common AEs, is better when TKIs are used as monotherapy vs. in combination with immunological agents. To confirm these findings, further research is needed, including large RCTs. [ABSTRACT FROM AUTHOR]

Pathologies of the pineal gland region are frequently encountered in daily neurosurgical practice. It is important to remember that, besides usually asymptomatic pineal gland cysts, neoplasms of a different origin may also occur in this region. The rarity of the most dangerous lesions - pineal gland apoplexy and pineal tumors - might cause problems with proper diagnosis and treatment. Their occurrence is commonly associated with symptomatic hydrocephalus caused by aqueductal stenosis. Currently, in such cases, endoscopic procedures, including endoscopic third ventriculostomy (ETV), are commonly and widely chosen as treatment options. Endoscopic procedures not only enable decompression of hydrocephalus but also further diagnosis of its cause. Herein, we present 3 case reports of endoscopic treatment with ETV performed in patients with hydrocephalus related to pineal region pathologies. [ABSTRACT FROM AUTHOR]

A rise in the incidence of infections with severe acute respiratory syndrome coronavirus 2 has sparked the search for protective strategies against the new pathogen. It is known that individual food components can interact with different immune cells, modulating the immune response of the body. The aim of this study was to develop an index assessing the immunomodulatory potential of diet (POLA index) and to test its utility for the prediction of coronavirus disease 2019 (COVID-19) in a group of healthy young people following a traditional or vegetarian diet. Data on body composition, anthropometric measurements, physical activity, dietary intake, and gut microbiota were obtained from 95 adults (mean age, 34.66 ± 5.76 years). There was a strong correlation between the dietary inflammatory index and the POLA index (r = 0.90; p < 0.0001). Based on Cohen's kappa statistic, there was a good agreement in qualitative interpretation between the two indices (kappa = 0.61; p < 0.0001). People on a diet with beneficial immunomodulatory effects had a lower risk of COVID-19 of approximately 80%, as compared with those on a diet with highly unbeneficial immunomodulatory effects. In daily practice, the POLA index might serve as a useful tool for dietitians to identify individuals whose diet is deficient in ingredients for optimal immune system function and change their dietary behavior to ensure optimal immune function that reduces the risk of infection. [ABSTRACT FROM AUTHOR]

Introduction: In Poland, busulfan conditioning is used for allogeneic hematopoietic stem cell transplantation (allo--HSCT). Cost-utility analyses comparing alternative conditioning regimens in patients undergoing allo-HSCT have not been conducted so far. Material and methods: A United Kingdom-based partitioned survival model was adapted to the Polish setting to compare treosulfan to low-dose busulfan conditioning regimen from the public payer's perspective in Poland. Patient characteristics, overall survival (OS), event-free survival (EFS), and the rate of adverse events were obtained from the randomized MC-FludT.14/L trial. Parametric survival models of up to 5 years (the cure threshold), with subsequent mortality defined using survival of the general population of Poland adjusted for cancer survivors, were used to extrapolate OS and EFS beyond the trial duration. Published utilities were adjusted for age using age-dependent general population utilities. The costs of treatment, adverse events, and inpatient/outpatient care were assessed via official remuneration schemes. Results: Treosulfan-based conditioning outperformed low-dose busulfan, i.e. it was more effective with incremental quality-adjusted life years (QALY) of 0.78 and less expensive by 1,139 PLN per patient over the lifetime horizon. Deterministic sensitivity analyses revealed treosulfan was highly cost-effective (i.e. incremental cost-utility ratio was lower than the gross domestic product per capita in Poland) compared to low-dose busulfan, if most uncertain parameters are changed or alternative scenarios are implemented. The probability of treosulfan being cost-effective with a threshold of 155,514 PLN was 99.6%. Conclusions: Compared to low-dose busulfan, treosulfan is a highly cost-effective conditioning regimen for allo-HSCT patients ineligible for standard conditioning regimens. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the impact of selected legislative initiatives and their implementation for off-patent medicinal products in Slovakia compared with the rest of the Visegrád Group (V4 countries). Methods: We analyzed the development of applications for the reimbursement of generic and biosimilar drugs. Particular emphasis was placed on a) the availability and penetration of biosimilars from 2006 to 2020 in Slovakia, b) a comparative analysis of biosimilars in V4 countries based on the national reimbursement lists of medicinal products for August 2021. Data relating to the sales of generic and biosimilar medicines in Czechia, Hungary, Poland, and Slovakia were based on the IQVIA MIDAS MAT July 2021. Results: The number of applications for the reimbursement of generic drugs decreased from 296 in 2016 to 165 in 2020. In financial terms, the sales of generic medicines in Slovakia increased from 21.7% in 2015 to 22.3% in 2020. Over the same period, the sales of generic drugs in Poland fell from 40.4% in 2015 to 35.0% in 2020, from 26.2 to 22.1% in Hungary, and from 29.6 to 20.4% in Czechia. When considering the 66 biosimilars registered by the European Medicines Agency 38 drugs (58%) were available on the Slovak market as of August 1, 2021; this compared to 32 drugs (48%) in Poland, 38 drugs (58%) in Hungary, and 40 drugs (61%) in Czechia. In financial terms, the sales of biosimilars in Slovakia increased from 0.94% in 2015 to 2.00% in 2020. Over the same period, the sales of biosimilars in Poland increased from 0.59% in 2015 to 1.29% in 2020, from 0.72 to 2.23% in Hungary, and from 0.76 to 2.15% in Czechia. Conclusion: To intensify the use of generic and biosimilar medicines, we suggest the comprehensive re-evaluation of combinations of the three-threshold entry, the amount of mandatory price reductions, and external reference pricing requirements (as the average of the three lowest prices among the official prices of a medicinal product in other Member States) for generic and biosimilar drugs. We also suggest cancellation of the exception from the fixed co-payment of the insured. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the sensitivity and specificity of computed tomography (CT) scans of the chests of patients with the reference reverse-transcription real-time polymerase chain reaction (RT-PCR) in early diagnosis of COVID-19. A systematic review with meta-analysis for numerical outcomes was performed, including 10 studies (6528 patients). High risk of systematic bias (spectrum bias) was demonstrated in all studies, while in several studies research information bias was found to be possible. The sensitivity of CT examination ranged from 72% to 98%, and the specificity from 22% to 96%. The overall sensitivity of the CT scan was 91% and the specificity 87% (95% CI). Overall sensitivity of the RT-PCR reference test was lower (87%) than its specificity (99%) (95% CI). No clear conclusion could be drawn on the rationale of using CT scanning in the early diagnosis of COVID-19 in situations when specific clinical symptoms and epidemiological history would indicate coronavirus infection. The sensitivity of the CT test seems to be higher than that of the RT-PCR reference test, but this may be related to the mode of analysis and type of material analysed in genetic tests. CT scanning could be performed in symptomatic patients, with a defined time interval from symptom onset to performing CT or RT-PCR, and it should be explicitly included as an additional procedure when initial coronavirus genetic test results are negative, while clinical symptoms and epidemiological history indicate possible infection. However, a reference test showing the presence of coronavirus genetic material is essential throughout the diagnostic and treatment process. [ABSTRACT FROM AUTHOR]

Background: It is essential to provide safe healthcare in complex, difficult, and quickly changing conditions. The quality of healthcare services directly influences the safety of both the patients and staff. Understanding healthcare staff attitudes toward safety in the healthcare delivery context is foundational for building a culture of safety. Aim of the work: To adapt, via a structured translation methodology, the Safety Attitudes Questionnaire–Short Form (SAQ-SF), which assesses how employees of the health care sector perceive the safety climate in their workplace, to the Polish context. Methods: Using a content validation approach to structure the translation process, we tested and psychometrically analysed the translated SAQ-SF. The sample comprised 322 employees of a district hospital (second referral level, which ensures 24/7 emergency care services) in Poland. Results: The reliability of the sub-scales of the Polish version of the SAQ-SF ranged from 0.66 to 0.95. The discriminatory power of particular SAQ items ranged between 0.02 and 0.90. For 6 out of the 8 scale dimensions, the questions with the highest factor loadings were those measuring the same dimensions of the safety climate, according to the original scale. Conclusions: The Polish version of the SAQ-SF (SAQ-SF-PL) meets the criteria of psychometric and functional validation as well as demonstrates good reliability as a measure of patient safety culture in the Polish context. The SAQ-SF-PL is an instrument that enable a valid and reliable assessment of patient safety climate in the Polish healthcare facilities and identify opportunities for improvement. International comparisons will also become easier. [ABSTRACT FROM AUTHOR]

Introduction: An anterior approach is most commonly used in procedures performed in cases of degenerative cervical spine disease (DCSD). Although generally considered safe, they are not free of complications that may result in the need for reoperation. The aim of the study is to analyse causes of reoperation via the same approach for DCSD in patients who have previously undergone one of the anterior cervical approaches. Materials and methods: Of the 2,794 patients managed with a surgical procedure performed from an anterior approach, a total of 38 were reoperated on via the same anterior route between year 2004-2019 at a single tertiary centre. Retrospective assessment was conducted based on medical records and radiological imaging. Subjects were grouped into 2 categories: early revision surgeries (within 90 days of the 1st procedure) and late revision surgeries (after 90 days). Results: The incidence of same-route reoperation was 1.36%. Late reoperations were over twice as frequent as early ones (n = 26 vs n = 12). The main cause for reoperation in the late group was adjacent segment disease (ASD; n = 25, 96.15%) whereas in the early group, persistent stenosis and implant dislocation were equally prevalent (each n = 3, 27.3%). The reoperations which were conducted earliest were due to emergent post-operative prevertebral hematomas (n = 2, 16.67%). Conclusion: The risk of needing a same-route reoperation after anterior approaches in DCSD is relatively low with late revisions being more prevalent. Adjacent segment disease is the most common cause. Implant dislocation as well as persistent spinal canal stenosis are the main causes behind early revisions. [ABSTRACT FROM AUTHOR]