Safety Profile of First-Line Targeted Therapies in Elderly and/or Comorbid Chronic Lymphocytic Leukaemia Patients (Unfit Subpopulation). A Systematic Review and Network Meta-Analysis.

This systematic literature review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1-5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1-5. The use of Bruton's tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities.

Clinical aspects of reimbursement policies for orphan drugs in Central and Eastern European countries.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications. Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs. Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a "strong" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a "moderate" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the "positive HTA recommendation guarantees reimbursement" policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001). Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.

Provision of special diets to children in public nurseries and kindergartens in Kraków (Poland).

Background: A specialized diet could be due to an allergy or other medical needs and also religious or cultural reasons. This study aimed to assess the availability and provision of special diets in kindergartens and nurseries financed by the Municipality of Kraków. Methods: This observational cross-sectional study was based on a diagnostic survey carried out using the Computer-Assisted Web Interview method and addressed to the managers of nurseries (n = 21) and kindergartens (n = 71) and, separately, to the parents of children attending these facilities (n = 1,096). Non-parametric tests were applied for an unadjusted comparison between children at nurseries and those at kindergartens. Results: Children with particular dietary requirements received special diet meals in 95.2% of nurseries and 60.5% of kindergartens. The availability of special diets was associated with the type of facility (p = 0.001), the number of children who ate in the facility (p = 0.032), and the daily cost of meals served to children (p = 0.009). The cost of meals was higher in kindergartens that offered special diets vs. those that did not offer such diets (p < 0.001). According to parents, 96.4% of the total number of children ate meals served in the facilities. In nurseries, 16.1% of children were on a special diet (as per the doctor's recommendations in 11.7% of cases and according to parents' own choice in 4.4%). In kindergartens, a special diet was served to 12.7% of children (doctor's recommendations, 8.5%; parents' own choice, 4.2%). The most common reason for using a special diet was food allergy (8.2% of children in nurseries and 5.8% of children in kindergartens). It was reported more often by the parents of children attending nurseries than by the parents of children attending kindergartens (8.0% vs. 4.2%, p = 0.007). The requirement for a special diet was found to be associated with the age of children (p < 0.033) and the use of oral treatment for chronic disease (p < 0.001). Conclusion: Providing special diets for children is better in nurseries than in kindergartens. Legal regulations are urgently needed to ensure equal access to adequate nutrition for all children with special dietary needs in childcare facilities.

Evidence for external beam radiotherapy in mediastinal Hodgkin and non-Hodgkin lymphoma - systematic review.

INTRODUCTION AND OBJECTIVE: Proton beam therapy (PBT) provides the opportunity for a more localized delivery of high energy protons and may reduce the damage to healthy tissues and vital organs. The aim of this review was to assess the effects of proton therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma treated with mediastinal irradiation. REVIEW METHODS: A systematic search of EMBASE, MEDLINE via OVID and Cochrane Library was conducted in May 2022 according to PRISMA guidelines to identify relevant data on the efficacy and toxicity of proton beam therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Of 566 screened abstracts (430 after de-duplication) 11 studies with a total of 529 patients were included. All studies were case series published between 2011-2021. Median range of follow-up time was 15-63.6 months. The overall survival (OS) for 2 years varied from 91% - 98% for 5 of the included studies. Three of the included studies had favourable outcomes with 2-year progression-free survival (PFS) ranging from 73% - 94%. Skin reaction, oesophagitis and fatigue were found to be the most common grade 1 and grade 2 toxicities. No acute or late grade 4 and higher toxicities/adverse events were observed. SUMMARY: There are data indicating that PBT may to be an effective treatment against mediastinal Hodgkin and non-Hodgkin lymphoma. Because all the studies were case series, the authors of this review have little confidence in the evidence. There remains a need for well-designed randomized controlled trials to inform about the optimal approach to proton irradiation in HL and NHL.

Potential use of psilocybin drugs in the treatment of depression.

INTRODUCTION: Depression is a common disabling psychiatric disorder, which - in extreme cases - may lead to suicide if untreated or inadequately treated. Despite the availability of various treatments for depression, including pharmacotherapy, there is still a need to search for new agents with higher effectiveness and faster onset of action, especially for patients with treatment-resistant depression. AREAS COVERED: A substance that has attracted considerable attention for nearly a decade is psilocybin, a natural psychedelic found in psilocybin mushrooms. In this study, we evaluated the efficacy and safety of psilocybin in the treatment of depression, based on pivotal randomized clinical trials. Moreover, we used findings from observational studies regarding recreational use. We also looked at ongoing clinical trials and discussed the registration status and clinical potential of the drug. EXPERT OPINION: Clinical phase I-II trials published to date reported promising results for psilocybin in the treatment of patients with major depressive disorder and treatment-resistant depression, in a relatively short time after administration. However, before psilocybin is approved for use and administered to patients with depression, the results of large ongoing phase III clinical trials are needed to confirm its efficacy and safety and to change the way it is perceived by physicians and patients.

The Potential of Scopolamine as an Antidepressant in Major Depressive Disorder: A Systematic Review of Randomized Controlled Trials.

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.

Comparative safety of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma: a systematic review and network meta-analysis.

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.

Indirect Costs of Inflammatory Bowel Diseases: A Comparison of Patient-Reported Outcomes Across 12 European Countries.

BACKGROUND: National studies report a high variability of indirect costs of inflammatory bowel disease (IBD). In this study, selected aspects of the societal burden of IBDs were compared between 12 European countries. METHODS: A questionnaire-based study among adult patients with IBD was performed. Data on patient characteristics, productivity loss, and informal care were collected. The costs of productivity loss were assessed from the social perspective. The cost of absenteeism and presenteeism was valuated using the gross domestic product per worker. Informal care was measured by time inputs of relatives and friends to assist patients. Productivity loss among informal caregivers outside their paid work was valuated with the average wage. The results were adjusted for confounders and multiplicity. RESULTS: Responses from 3687 patients (67% employed) were analyzed. Regular activity (outside paid work) impairment did not differ between countries, but a significant difference in informal care and productivity loss was observed. There were no differences in indirect costs between the types of IBD across the countries. The mean annual cost of absenteeism, presenteeism, and informal care varied from €1253 (Bulgaria) to €7915 (Spain), from €2149 (Bulgaria) to €14 524 (Belgium), and from €1729 (Poland) to €12 063 (Italy), respectively. Compared with patients with active disease, those with IBD in remission showed a lower indirect cost by 54% (presenteeism, P < .001) or 75% (absenteeism, informal care, P < .001). CONCLUSIONS: The study showed a high relevance of the indirect cost of IBD in the context of economic evaluation, as well as a between-country variability of work-related impairment or informal care.

The study showed a high relevance of the indirect cost of inflammatory bowel disease in the context of economic evaluation, as well as a between-country variability of work-related impairment or informal care.

Out-of-pocket expenses of patients with inflammatory bowel disease: a comparison of patient-reported outcomes across 12 European countries.

BACKGROUND: There is a high variability of out-of-packet patient costs of inflammatory bowel diseases (IBDs), but the issue is not widely recognised. Therefore, we compared patient costs of IBDs between 12 European countries. METHODS: A questionnaire-based study was conducted among adult patients with IBD. Data on patient characteristics and out-of-pocket expenses were anonymously collected. Ordered logit regression models were used to analyse the responses provided by patients. The results were adjusted for confounders and multiplicity. RESULTS: The questionnaires obtained from 3687 patients were analysed. Patients with comorbidities and active disease indicated higher out-of-pocket expenses than those without comorbidities and with disease in remission, respectively. Compared with other IBD, patients with ulcerative colitis indicated higher expenses on medications prescribed or recommended by physicians [odds ratio (OR) 1.99, 95% CI 1.48-2.67]. Expenses on dietary supplements, special diet or equipment, ostomy pouches, and transportation to a medical facility differed slightly between patients at different ages and were lower among men than among women (OR 0.71, 95% CI 0.54-0.93). The expenses differed significantly between countries. An adjusted mean patient cost per month varied from €77 (patient with Crohn disease in remission from Denmark) to €376 (patient with active ulcerative colitis from Romania). Compared with active disease, patients with IBD in remission had a lower out-of-pocket cost by 29-62% (€10-€22 monthly; p < 0.001). CONCLUSIONS: The study revealed a high relevance of the out-of-pocket cost of IBD in the context of economic evaluation and a high variability of the cost between countries.

Proposition of a New POLA Index to Assess the Immunomodulatory Properties of the Diet and Its Relationship with the Gut Microbiota, Using the Example of the Incidence of COVID-19 in a Group of People without Comorbidities.

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.

Where do we go next in antidepressant drug discovery? A new generation of antidepressants: a pivotal role of AMPA receptor potentiation and mGlu2/3 receptor antagonism.

INTRODUCTION: Major depressive disorder remains a prevalent world-wide health problem. Currently available antidepressant medications take weeks of dosing, do not produce antidepressant response in all patients, and have undesirable ancillary effects. AREAS COVERED: The present opinion piece focuses on the major inroads to the creation of new antidepressants. These include N-methyl-D-aspartate (NMDA) receptor antagonists and related compounds like ketamine, psychedelic drugs like psilocybin, and muscarinic receptor antagonists like scopolamine. The preclinical and clinical pharmacological profile of these new-age antidepressant drugs is discussed. EXPERT OPINION: Preclinical and clinical data have accumulated to predict a next generation of antidepressant medicines. In contrast to the current standard of care antidepressant drugs, these compounds differ in that they demonstrate rapid activity, often after a single dose, and effects that outlive their presence in brain. These compounds also can provide efficacy for treatment-resistant depressed patients. The mechanism of action of these compounds suggests a strong glutamatergic component that involves the facilitation of AMPA receptor function. Antagonism of mGlu2/3 receptors is also relevant to the antidepressant pharmacology of this new class of drugs. Based upon the ongoing efforts to develop these new-age antidepressants, new drug approvals are predicted in the near future.

How Can We Optimize the Value Assessment and Appraisal of Orphan Drugs for Reimbursement Purposes? A Qualitative Interview Study Across European Countries.

Introduction: The expansion of orphan drug treatment at increasing prices, together with uncertainties regarding their (cost-)effectiveness raises difficulties for decision-makers to assess these drugs for reimbursement. The present qualitative study aims to gain better insight into current value assessment and appraisal frameworks for orphan drugs, and provides guidance for improvement. Methods: 22 European experts from 19 different countries were included in a qualitative survey, followed by in-depth semi-structured interviews. These experts were academics, members of reimbursement agencies or health authorities, or members of regulatory or health/social insurance institutions. Adopting a Grounded Theory approach, transcripts were analysed according to the QUAGOL method, supported by the qualitative data analysis software Nvivo. Results: Although participants indicated several good practices (e.g., the involvement of patients and the presence of structure and consistency), several barriers (e.g., the lack of transparency) lead to questions regarding the efficiency of the overall reimbursement process. In addition, the study identified a number of "contextual" determinants (e.g., bias, perverse effects of the orphan drug legislation, and an inadequate consideration of the opportunity cost), which may undermine the legitimacy of orphan drug reimbursement decisions. Conclusion: The present study provides guidance for decision-makers to improve the efficiency of orphan drug reimbursement. In particular, decision-makers can generate quick wins by limiting the impact of contextual determinants rather than improving the methods included in the HTA. When implemented into a framework that promotes "Accountability for Reasonableness" (A4R), this allows decision-makers to improve the legitimacy of reimbursement decisions concerning future orphan drugs.

Socio-Economic Factors Influencing the Use of Dietary Supplements by Schoolchildren from Malopolska Voivodship (Southern Poland).

The use of regular supplementation may be important in alleviating the potential effects of specific nutrient deficiencies. The aim of this cross-sectional study was to assess the socio-economic and lifestyle factors influencing the administration of dietary supplements to schoolchildren from the Malopolskie voivodship. The study was conducted in March-June 2018 on 332 healthy children and adolescents (187 boys, 145 girls) aged 7-14 from the city and municipality of Niepolomice and the city of Kraków. The mean age of the subjects was 10.35 + 1.64 years. In order to assess their diet, a questionnaire was completed, by the parents or the child, on the frequency of consumption of specific products and foods (Food Frequency Questionnaire, FFQ) with added questions on the supplements provided. In assessing nutritional status, basic anthropometric measurements were taken and the BMI index was analysed. To check which factors influenced the use of supplements among respondents, the odds ratio (OR) was calculated. Approximately one-third of the total number of subjects (33.8%) took dietary supplements, most often supplements containing vitamins D and C, followed by multivitamin supplements and omega-3 fatty acids. The least common supplements contained calcium and iron. Dietary supplement intake was significantly higher among children living in rural areas compared to city areas (39.3% vs. 26.5% of respondents; p = 0.0150), and among boys compared to girls (37.3% vs. 27.8%; p = 0.048). It was observed that children more often received dietary supplements in multigenerational families and in families where at least one parent did not work. This is related to the place of residence of the respondent. Awareness of the need for, and the safe use of, dietary supplements is necessary among parents of children and adolescents.

Opicapone as an add-on to levodopa for reducing end-of-dose motor fluctuations in Parkinson's disease: a systematic review and meta-analysis.

Aim: To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Patients: Levodopa-treated adults with Parkinson's disease. Material & methods: A systematic review and meta-analysis were conducted. Results: Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving opicapone increased the frequency of dyskinesia. Conclusion: Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.

Comparative safety of high-efficacy disease-modifying therapies in relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis.

OBJECTIVE: This study aimed to compare the safety profile of high-efficacy disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, as well as a potentially high-efficacy DMT, ponesimod, in adult patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included randomized controlled trials (RCTs) with at least 48-week follow-up investigating the use of natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, and ponesimod, as well as other DMTs, in adult patients with RRMS. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The Cochrane Collaboration tool to assess the risk of bias for RCTs was used. RESULTS: A total of 33 RCTs were included in the systematic review and NMA. A higher rate of adverse events (AEs) was revealed for alemtuzumab versus all other high-efficacy DMTs; for alemtuzumab (average probability of an event: 98.2%) versus placebo (86.2%); for cladribine (3.5 mg; 90.5%) versus ozanimod (1 mg; 84.2%) and placebo; as well as for ocrelizumab (95.5%) versus ozanimod, ofatumumab (88.9%), fingolimod (87.4%), natalizumab (82.8%), and placebo. No significant differences were found between drugs in terms of serious AEs except for cladribine (3.5 mg, 17.3%) versus ocrelizumab (10.3%) and ofatumumab (16.6%) versus ocrelizumab. Significant differences in AEs leading to the discontinuation of study drug were found only for ponesimod (10.1%) versus alemtuzumab (12 mg, 3.0%) and placebo (4.2%). No differences were found in terms of upper respiratory tract infections, nasopharyngitis, fatigue, and nausea between individual high-efficacy DMTs as well as between DMTs and placebo. The results of the NMA indicated a higher risk of infections for alemtuzumab (12 mg) versus ocrelizumab, for cladribine (3.5 mg) versus ofatumumab and placebo, and for ofatumumab versus placebo. For serious infections and urinary tract infections, a significant increase was found only for alemtuzumab (12 mg) versus ocrelizumab, while no differences were found between the other DMTs or between DMTs and placebo. Headache was more common for alemtuzumab (12 mg) as compared with all the other high-efficacy DMTs and placebo, as well as for cladribine versus natalizumab and fingolimod versus natalizumab. CONCLUSION: The commonly reported AEs are generally similar among high-efficacy DMTs. However, based on P scores for most analyzed endpoints, natalizumab and ocrelizumab were shown to be the safest DMTs. Considering the limitations of indirect comparisons, further research is needed to confirm our findings, preferably head-to-head RCTs and large observational studies.

Associations of Nutritional Behavior and Gut Microbiota with the Risk of COVID-19 in Healthy Young Adults in Poland.

The numerous consequences of the coronavirus disease 2019 (COVID-19) pandemic in healthy young people and the lack of clarity as to the long-term disease outcomes have spurred the search for risk factors for SARS-CoV-2 infection. We aimed to evaluate the associations of nutritional behaviors, gut microbiota, and physical activity with the risk of COVID-19 in healthy young nonobese people. 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). A balanced diet rich in vegetables and fruit, including nuts, wholegrain cereal products, and legumes, covers the need for vitamins and minerals. Such a diet can be an effective measure to reduce the risk of COVID-19 in nonobese healthy physically active young people with normal immune function. People with balanced diet and an average daily consumption of >500 g of vegetables and fruit and >10 g of nuts had an 86% lower risk of COVID-19 compared with those whose diet was not balanced and who consumed lower amounts of these products. It is well documented that proper nutrition, physical activity, and maintenance of normal weight facilitate good health by ensuring optimal immune function. The beneficial effects of these interventions should be strongly emphasized during the COVID-19 pandemic.

The Impact of Reimbursement Practices on the Pharmaceutical Market for Off-Patent Medicines in Slovakia.

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.

Chest computed tomography versus RT-PCR in early diagnostics of COVID-19 - a systematic review with meta-analysis.

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.

Cultural adaptation of the Safety Attitudes Questionnaire - Short Form (SAQ-SF) in Poland.

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.

Health technology assessment and reimbursement policy for oncology orphan drugs in Central and Eastern Europe.

BACKGROUND: The reimbursement of orphan drugs (OD) is an increasingly important for country policymakers, and still insufficiently understood, especially in Central and Eastern Europe. The aim of this research was to provide a comprehensive description of country-specific health technology assessment (HTA) policies as well as evaluate the percentage of HTA recommendations and reimbursement decisions for oncology OD. In addition, the study was designed to elucidate the impact of reimbursement of these drugs on the public budget and the agreement between HTA recommendations and reimbursement decisions in the analysed countries. A questionnaire survey was used to collect data on the reimbursement status, HTA recommendation, marketing authorisation, and public expenses on reimbursement in 2014, 2015, and 2016 for all oncology drugs with an orphan designation by the European Medicine Agency in 2017 in Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovakia. The agreement between the HTA recommendation and reimbursement status was assessed using the kappa coefficient. The Pearson's correlation was used to analyse the relationship between gross domestic product (GDP) and GDP per capita and reimbursement expenses. RESULTS: A total of 36 drugs were analysed (25% conditionally approved; 5.56% approved under exceptional circumstances). The share of reimbursed drugs ranged from 11.11% in Latvia to 41.67% in Poland. The highest share of positive recommendations was observed for Bulgaria and Estonia (36.11%), and the lowest, for Latvia (11.11%). The agreement varied from 0.4 for Poland to 1 for Latvia, Hungary, and Slovakia. Expenses were correlated with GDP (0.95 [0.81-0.99]), and not with GDP per capita (0.54 [- 0.136 to 0.873]). Expenses per capita were not correlated with GDP per capita (0.52 [- 0.15 to 0.87]). CONCLUSIONS: In Hungary, Latvia, and Slovakia, a positive recommendation was associated with a reimbursement, and a negative one, with the lack of reimbursement. The reimbursement of oncology OD is associated with a growing burden for public budget, and the expenses are correlated with the total GDP. The highest share of drugs with any recommendation was observed in Poland, and the lowest, in Latvia and Romania. The share of reimbursed drugs was the lowest in Latvia and the highest in Poland.