Is Balneotherapy Protective Against Oxidative Stress? A Pilot Study.

BACKGROUND/AIM: This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. PATIENTS AND METHODS: Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol. RESULTS: The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049). CONCLUSION: The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.

Association of antibiotic-consumption patterns with the prevalence of hematological malignancies in European countries.

Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009-2019) and the incidence rate of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0.029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0.001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = - 0.460, p = 0.011), and quinolone (r = - 0.380, p = 0.038). The incidence of LEU did not show any positive or negative association with any antibiotic classes using Spearman calculation. Multivariate ordinal logistic regression (OR) indicated increased risk between HL and the total consumption of systemic antibiotics (J01 p: 0.038), and tetracyclin (J01A p: 0.002). Similarly, increased risk has been detected between the MM and tetracyclin (J01A p: 0.02), and narrow spectrum, beta-lactamase resistant penicillin (J01CF p: 0.042) and decreased risk between cephalosporin and MM (J01D p:0.022). LEU showed increased risk with the consumption of macrolides (p: 0.047).

Publication of clinical trials on medicinal products: follow-up on trials authorized in Hungary.

BACKGROUND: Clinical research should provide reliable evidence to clinicians, health policy makers, and researchers. The reliability of evidence will be assured once study planning, conducting, and reporting of results are transparent. The present research investigates publication rates, time until publication, and characteristics of clinical trials on medicinal products associated with timely publication of results, measures of scientific impact, authorship, and open access publication. METHODS: Clinical trials authorized in Hungary in 2012 were followed until publication and/or June 2020. Corresponding scientific publications were searched via clinical trial registries, PubMed (MEDLINE), and Google. RESULTS: Overall, 330 clinical trials were authorized in 2012 of which 232 trials were completed for more than 1 year in June 2020. The proportion of industry initiation was high (97%). Time to publication was 21 (22) months [median (IQR)]. Time to publication was significantly shorter when trials involved both European and non-European countries (26 vs 69 months [median]; hazard ratio = 0.38, 95% CI 0.22-0.66, p< 0.001), and were registered in both EU CTR and clinicaltrials.gov (27 vs 88 months; hazard ratio = 0.24, 95% CI 0.11-0.54; p< 0.001) based on survival analyses. A significant amount (24.1%) of unpublished clinical trial results were accessible in a trial register. The majority of available publications were published "open access" (70.93%). A minority of identified publications had a Hungarian author (21.5%). CONCLUSIONS: We encourage academic researchers to plan, register and conduct trials on medicinal products. Registries should be considered as an important source of information of clinical trial results. Publications with domestic co-authors contribute to the research output of a country. Measurable domestic scientific impact of trials on medicinal products needs further improvement.

Inverse association between use of broad spectrum penicllin with beta-lactamase inhibitors and prevalence of type 1 diabetes mellitus in Europe.

Increasing incidence of type 1 diabetes is supposed to be induced by environmental factors. Microbiome modulated by antibiotics seems to serve as one of the environmental factors which could influence the development of T1DM. Mitochondria, as autochthonous environmental bacteria living in our cells, and other bacteria share many common enzymes including beta-lactamases and it is supported by evidence that some beta-lactamase inhibitors are able to interact with counterpart enzymes. Thus, antibiotics may utilize two different pathways influencing the development of T1DM; one through modulation of microbiome and a second one via the interaction of mitochondrial enzymes. Data of consumption of penicillin (both narrow and broad spectrum) and beta-lactamase inhibitors in 30 European countries were collected from the database of the European Centre for Disease Prevention and Control. These data were correlated with the prevalence reported by the International Diabetes Federation (2019) referring to type 1 diabetes in Europe. No correlation was found between total penicillin consumption or use of broad spectrum penicillin and the prevalence of type 1 diabetes. Nevertheless, broad spectrum penicillin, in combination with beta-lactamase inhibitor, was in inverse correlation with the prevalence of type 1 diabetes (r = - 0.573, p = 0.001). On the other hand, narrow spectrum penicillin was in positive correlation with type 1 diabetes (r = 0.523, p = 0.003). Prevalence of type 1 diabetes showed an inverse correlation with the use of beta-lactamase inhibitors and a positive one with that of narrow spectrum penicillin. Such a detailed analysis has not so far been provided referring to the penicillin group. In the background of this association either microbiomal or direct mitochondrial effects can be supposed.

A New and Validated, Randomised, Controlled Placebo Water Development Trial for Medicinal Water-based Research.

BACKGROUND/AIM: To develop and validate an easy-to-use and cheap method capable of producing placebo from tap water for medicinal water efficacy trials. PATIENTS AND METHODS: Patients were divided into two groups, medicinal water and tap water group. A single 20-minute-long treatment was performed in bathtubs. Patients were asked four times during the bath to tell if they were treated with medicinal water, tap water, or could not decide. Patients were scored, one point was given for each correct answer. RESULTS: A total of 174 patients were enrolled. No significant differences were found either between the average scores or the answers of the two groups. Being familiar with the Harkány medicinal water did not influence the rate of correct answers either. There was no statistically significant difference in the number of changes of opinions between the two groups. CONCLUSION: The used method is appropriate for producing a validated placebo from tap water.

Dominant Antibiotic Consumption Patterns Might Be Associated With the Prevalence of Multiple Sclerosis in European Countries.

BACKGROUND/AIM: With a prevalence of 50-300 per 100,000 people, about 2.3 million people are estimated to live with multiple sclerosis (MS) globally. The role of antibiotics in the development, or prevention of MS is controversial. We aimed to elucidate the association between antibiotic consumption and MS. PATIENTS AND METHODS: Pearson statistical comparisons were performed between the annual average antibiotic consumption patterns expressed in Defined Daily Dose/1,000 inhabitants/Day of the antibiotic consumption for the years of 1997-2018 in 30 European countries, with the respective prevalence of MS estimated for 2016. RESULTS: A positive correlation (promoting effect) has been observed between narrow spectrum penicillin (r=0.636) and tetracycline (r=0.412) consumption with MS prevalence. CONCLUSION: Countries, with high consumption of narrow spectrum penicillin and tetracycline, experience a higher prevalence of MS than other countries.

Antibiotic Consumption Patterns in European Countries May Be Associated with the Incidence of Major Carcinomas.

The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997-2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with "augmenting" properties and with less consumption of antibiotics with "inhibitory" properties.

Self-reported attitudes, knowledge and skills of using evidence-based medicine in daily health care practice: A national survey among students of medicine and health sciences in Hungary.

In order to map attitudes, knowledge and skills related to evidence-based medicine (EBM) in students of medical and health sciences faculties, we performed an online survey during the spring semester 2019 in all medical and health sciences faculties in Hungary. In total, 1080 students of medicine and 911 students of health sciences completed the online questionnaire. The attitude towards EBM was generally positive; however, only a small minority of students rated their EBM-related skills as advanced. There were large differences in the understanding of different EBM-related terms, with 'sample size' as the term with the highest (65%) and 'intention-to-treat analysis' with the lowest (7%) proportion of medical students being able to properly explain the meaning of the expression. Medical students who already participated in some EBM training rated their skills in searching and evaluating medical literature and their knowledge of EBM-related terms significantly better and had a more positive attitude towards using EBM in the practice than students without previous EBM training. EBM trained medical students were more likely to choose online journals (17.5% compared to 23.9%, p<0.05) and professional guidelines (15.4% compared to 6.1%, p<0.001) instead of printed books (33.6% compared to 52.6, p<0.001) as the main source of healthcare information retrieval and used Pubmed/Medline, Medscape and the Cochrane Library to a significant higher rate than students without any previous EBM training. Healthcare work experience (OR = 1.59; 95% CI = 1.01-2.52), conducting student research (OR = 2.02; 95% CI = 1.45-2.82) and upper year university students (OR = 1.65; 95% CI = 1.37-1.98) were other factors significantly influencing EBM-related knowledge. We conclude that the majority of students of medical and health sciences faculties are keen to acquire EBM-related knowledge and skills during their university studies. Significantly higher EBM-related knowledge and skills among EBM trained students underline the importance of targeted EBM education, while parallel increase of knowledge and skills with increasing number of education years highlight the importance of integrating EBM terminology and concepts also into the thematic of other courses.

Evidence for the therapeutic effect of the organic content in Szigetvár thermal water on osteoarthritis: a double-blind, randomized, controlled clinical trial.

The therapeutic effects of mineral waters have been attributed to the inorganic components alone; however, biologically active organic components are also present. We aimed to investigate whether the healing effect of Szigetvár thermal mineral water could relate to the organic matter in patients suffering from osteoarthritis of the hips and the knees. XAD macroreticular resins were used to prepare the organic fraction. Patients received a 30-min thermal water (34 °C) treatment in a bath tub, five times a week for 3 weeks. After randomization, patients were divided into three groups: tap water, mineral water, and organic fraction group. Primary outcomes were range of movement (ROM), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and visual analog scale (VAS) for pain severity, and the Short Form 36 (SF-36) questionnaire was used. These scores and indices were measured at baseline, after the last treatment, and at the end of the 3-month follow-up period. Seventy-four patients (age 67.3 ± 4.48 years) were enrolled: tap water n = 24, mineral water n = 26, and organic fraction n = 24. Treatment with the redissolved organic fraction significantly improved ROM, WOMAC, and SF-36 scores compared to the tap water. Our clinical trial provided evidence for the beneficial health effects of the organic fraction of Szigetvár medicinal water.

Improving asylum seekers' health awareness in a Hungarian refugee reception centre.

Due to its long border of the European Union Schengen Area, Hungary has long been affected by the rapidly growing inward migration towards the EU, which has become more acute in recent years. Inadequate access to healthcare among migrants has been widely reported and this may be due to a vast array of factors and may result in poorer health outcomes. Between August 2014 and April 2015 a questionnaire survey was conducted among migrants from a range of countries residing in the largest Hungarian refugee reception centre to establish participants' health knowledge and access to healthcare in Hungary (medical assessment, vaccination, etc.). The survey was complemented with an educational program which aimed to increase participants' awareness of healthcare provision and to promote the prevention of the infectious diseases that are common in Europe. The results showed that half the participants (52%) had no information of healthcare provision and the majority (61%) did not participate in any medical assessment since arriving in the reception centre. Since under-immunization may be a potential risk for the re-emergence of vaccine-preventable diseases for recipient countries, it was alarming that a significant proportion of African participants (21%) reported not having received any childhood vaccinations. Data demonstrated deficiencies in participants' health knowledge and also an urgent need to address mental health problems of arriving migrants. This article offers a valuable insight into the role of health educational interventions conducted for asylum seekers in refugee reception centres and discusses a number of practical application aspects for future educational programs.

Novel radiomics evaluation of bone formation utilizing multimodal (SPECT/X-ray CT) in vivo imaging.

Although an extensive research is being undertaken, the ideal bone graft and evaluation method of the bone formation draw still a warranted attention. The purpose of this study was to develop a novel multimodal radiomics evaluation method, utilizing X-ray computed tomography (CT) and single photon emission computed tomography (SPECT) with Tc-99m-Methyl diphosphonate (Tc-99m-MDP) tracer. These modalities are intended to provide quantitative data concerning the mineral bone density (after evaluation it is referred to as opacity) and the osteoblast activity, at the same time. The properties of bone formation process within poly (methyl methacrylate)-based bone cement graft (PMMA) was compared to that of albumin coated, sterilized, antigen-extracted freeze-dried human bone grafts (HLBC), in caudal vertebrae (C5) of rats. The animals were scanned at 3 and 8 weeks after surgery. In both groups, the mean opacity increased, while the mean Tc-99m-MDP activity decreased. The later parameter was significant (n = 4, p = 0.002) only in HLBC group. The linear regression analysis of PMMA-treated group variables (mean opacity increase; mean Tc-99m-MDP activity decrease), revealed a negative correlation with the medium strength (r = 0.395, p = 0.605). Whereas, it showed strong positive correlation when HLBC group variables were analyzed (r = 0.772, p = 0.012). These results indicate that using HLBC grafts is advantageous in terms of the osteoblast activity and bone vascularization over PMMA cement. Using this regression analysis method, we were able to distinguish characteristics that otherwise could not be distinguished by a regular data analysis. Hence, we propose utilizing this novel method in preclinical tests, and in clinical monitoring of bone healing, in order to improve diagnosis of bone-related diseases.

Inulin-Type Fructan Supplementation of 3- to 6-Year-Old Children Is Associated with Higher Fecal Bifidobacterium Concentrations and Fewer Febrile Episodes Requiring Medical Attention.

Background: Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants. Objectives: The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota. Methods: 142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24. Results: In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups. Conclusions: Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355.

Clinical improvement of patients with osteoarthritis using thermal mineral water at Szigetvár Spa-results of a randomised double-blind controlled study.

Since 1966, Szigetvár in Hungary is well recognised as a thermal spa. Many patients suffering from rheumatic diseases are treated with its thermal mineral water. Our objective was to investigate the effects of a 3-week-long outpatient balneotherapy-based rehabilitation program on patients suffering from osteoarthritis of the hips and the knees. During the treatment period, patients received a 30-min underwater jet massage in a bath tub, five times a week. One patient group received jet massage in a bath tub containing mineral water; the other group received the same treatment in tap water. Primary outcomes were measured by range of movement of the involved joints and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Visual analogue scale (VAS) was applied to measure current severity of pain. Furthermore, quality of life was assessed using the Short Form 36 questionnaire (SF-36). Range of movement (ROM) score, Western Ontario and McMaster University Osteoarthritis Index and visual analogue scale were determined before the first treatment, after the last treatment and 3 months after the last treatment. SF-36 questionnaire was filled in before the first and after the last treatment. Fifty patients (17 male, 33 female mean age 66.7 ± 4.79 years) were enrolled. After randomisation, patients were divided into two groups: tap water n = 24 and mineral water n = 26. Treatment with the thermal mineral water of Szigetvár significantly improved ROM, WOMAC scores, and SF-36-scored quality of life of the patients. Our double-blind study provided evidence for the beneficial health effects of another Hungarian thermal mineral water masking the colour, odour and pH of the tap water and mineral water.

[Effectiveness of mindfulness-based cancer recovery (MBCR) program among Hungarian cancer patients]. / Éber, tudatos figyelemre épülo, a rákbetegséggel való megküzdést segíto program (MBCR) hatásvizsgálata magyar rákbetegek körében.

INTRODUCTION AND AIM: Employment of mindfulness-based programs and techniques in the treatment of cancer patients have spread exponentially in the past decade. A large number of studies have proved the effectiveness of the program in the reduction of stress symptoms, depression and anxiety, and the improvement of sleep and mood patterns. The present study was done at Firebird Foundation and examines the effectiveness of the complex, MBCR (mindfulness-based cancer recovery)-based psycho-social intervention in the treatment of cancer patients. METHOD: The experimental group consisted of 101 people with various types and states of cancer. The control group consisted of 72 adjusted people. We did measurements (PPS, HADS, FACT-G, POMS-SF, Freiburg Adaptation Questionnaire) before the intervention (T1), right after the 8-week intervention (T2), and 6 months after the intervention (T3). RESULTS: The experimental group showed significant improvement in the measured psychological variables, and in few aspects of life quality between T1 and T2. There was a decrease in levels of observed stress and depression, and an escalation in optimism and vitality. We found a decrease in depressive and minimizing coping scores as well. There was a significant improvement in two dimensions of quality of life, and all these positive changes remained present by the end of the follow-up period (T3). In the control group, we only found a significant increase in minimizing coping scores at the time of T3 measurements. This is the first impact assessment study done on cancer patients using MBCR techniques in Hungary. CONCLUSIONS: The MBCR program is a very effective psychosocial intervention among cancer patients; it has a long term significant impact on mood and quality of life. Orv Hetil. 2017; 158(33): 1293-1301.

Can the use of medical muds cause genotoxicity in eukaryotic cells? A trial using comet assay.

Despite the lack of knowledge of their exact effects, peloids (natural muds) are widely applied in clinical treatment and prevention of different diseases, especially in rheumatic and gynecological disorders or skin diseases. Primarily we have information on their inorganic components, but only limited data are available on the organic components and nothing on their mechanism of chemical action. The objective of the present study was to detect the DNA-damaging effects (possible genotoxic effect) of peloid samples using the single-cell comet assay on Long Evans rat lymphocytes, human lymphocytes, and Eisenia fetida coelomocytes. Rat and human lymphocytes were exposed to the in toto peloid samples, in vitro. The Eisenia cells were extracted from the coelom of animals kept in the intact peloid sample. An indicator derived from the DNA fluorescence intensity was used in the statistical evaluation. The predominantly organic (Hévíz) sample showed a significant alteration from the negative control in several cases, while the inorganic (Kolop) applied did not. A higher quantity of organic compounds may have an important role in the emergence of DNA damage. The results revealed that medical muds have not only positive health effects but can also contain substances with potential human toxicity risk. Our research provides essential steps towards the creation of a toxicity profile and the possible safe use of peloids as medicinal therapy.

Perception of Occupational Risks and Practices of Self-protection from Infectious Diseases Among Workers in Contact with International Migrants at Hungary's Border.

OBJECTIVE: The purpose of the present study was to investigate employees' self-assessments of their occupational risks and health awareness as well as their perception of preventive methods. We also aimed to collect data on employees' perception of some selected alarming signs and symptoms that may encourage them to take further actions (such as separation and calling an ambulance). PARTICIPANTS AND METHODS: Between April and June 2013, an anonymous questionnaire survey was conducted with the participation of 70 employees working with migrants (both health-care and non-health-care staff) in 10 Hungarian settlements: 4 border crossing points along the eastern Schengen borderline, 3 asylum detention centers and 3 reception centers. RESULTS: Our results demonstrated an increased perception of certain biological and mental health hazards at work among those working with migrants: 63.7% of the health-care workers and even 37.3% of the non-health-care staff come into contact with human secretions (feces, urine, saliva) "frequently" or "sometimes". Self-assessed awareness of the signs and symptoms of infectious diseases was poor: only 12.8% of participants evaluated their awareness as "good" or "very good". Threat of verbal violence may be considered a common mental risk at work for participants: 35% "sometimes" or "frequently" and 5% "always" face verbal violence during their work. The most commonly used preventive measures against infectious diseases included the use of gloves, masks and disinfectants; these were generally available to 70 to 80% of the workers and properly applied. CONCLUSIONS: Our results indicate considerable deficiencies in the participants' preparedness in respect to their occupational health-related issues. Since it is essential for those having daily physical contact with migrants during their work to be properly informed about the occupational health hazards and consequences that may be associated with international migration, their training programs urgently require further development. More comprehensive knowledge may improve the preventive attitudes of employees, and conscious application of preventive measures may contribute to better public and occupation health safety.