mRNA vaccines: The future of prevention of viral infections?

Messenger RNA (mRNA) vaccines against COVID-19 are the first authorized biological preparations developed using this platform. During the pandemic, their administration has been proven to be a life-saving intervention. Here, we review the main advantages of using mRNA vaccines, identify further technological challenges to be met during the development of the mRNA platform, and provide an update on the clinical progress on leading mRNA vaccine candidates against different viruses that include influenza viruses, human immunodeficiency virus 1, respiratory syncytial virus, Nipah virus, Zika virus, human cytomegalovirus, and Epstein-Barr virus. The prospects and challenges of manufacturing mRNA vaccines in low-income countries are also discussed. The ongoing interest and research in mRNA technology are likely to overcome some existing challenges for this technology (e.g., related to storage conditions and immunogenicity of some components of lipid nanoparticles) and enhance the portfolio of vaccines against diseases for which classical formulations are already authorized. It may also open novel pathways of protection against infections and their consequences for which no safe and efficient immunization methods are currently available.

Navigating the Shifts: Retrospective Analysis of Alcohol Consumption and its Predictors Across Pre-Pandemic, Lockdown, and Post-Pandemic Eras in Poland.

BACKGROUND Alcohol consumption is a serious health risk that affects both physical and mental health. It is one of the major risk factors in the development of non-communicable diseases. The aim of this study was to perform a retrospective analysis of alcohol consumption patterns, determine of predictors of alcohol addiction, and attempt to distinguish and compare the profiles of participants differentiated in terms of their preferences in the pre-pandemic, lockdown, and post-pandemic periods. MATERIAL AND METHODS A retrospective study was conducted with a computer-assisted web interview on a representative sample of Polish citizens. Primary outcomes were sociodemographic and COVID-19-related variables, preferences regarding the type and location of consumed alcohol, reasons for drinking, severity of addiction symptoms, loneliness, quality of life, and health level. RESULTS During the lockdown period, the percentage of people declaring abstinence increased, as well as people who, according to the Alcohol Use Disorders Identification Test (AUDIT) cut-off points, could be diagnosed with probable alcohol dependence. The strongest predictors of the severity of addiction symptoms were preferences regarding the type and place of alcohol consumption, with a high percentage of explained variance (>50%). The analysis of profiles differentiated in terms of the preferred type of alcohol consumed allowed for the identification of 7 different profiles, which differed in terms of AUDIT score, loneliness, quality of life, and level of health. CONCLUSIONS Patterns of alcohol consumption changed during the pandemic. Alcohol-related preferences are important from the public health perspective.

Vaccination of Ukrainian Refugees: Need for Urgent Action.

The unprovoked aggression of Russian military forces on Ukraine in February 2022 has caused a high influx of refugees, including children, to neighboring countries, particularly Poland. This caused additional pressures on the healthcare system and the need to meet challenges for public health, such as those related to infectious diseases. Here, we discuss the potential epidemiological risks associated with the war-induced influx of refugees (coronavirus disease 2019, measles, pertussis, tetanus, and poliomyelitis) and highlight the need for their swift management through institutional support, educational campaigns, counteracting antiscience misinformation, and pursuing vaccinations of refugees but also improving or maintaining good levels of immunization in populations of countries welcoming them. These are necessary actions to avoid overlapping of war and infectious diseases and associated public health challenges.

EFFICACY AND SAFETY OF CANDELABRA ALOE EXTRACT (ALOE ARBORESCENS MILL.) IN PREVENTION AND TREATMENT OF UPPER RESPIRATORY TRACT INFECTIONS OF VARIOUS AETIOLOGIES.

OBJECTIVE: The aim: To evaluate therapeutic effects of a product containing Aloe arborescens extract (AA) as the active substance in children aged 3-18 years with a diagnosed viral or bacterial upper respiratory tract infection and to assess their carers' satisfaction with the use of the product. The above-mentioned product is also indicated to control the loss of appetite. Thus, the study also assessed the effect of AA on this parameter. PATIENTS AND METHODS: Materials and methods: A total of 6764 patients (children aged 3-18 years) were included in the study, which was conducted by 279 paediatrics and family medicine specialists (or being in the course of specialisation) from 237 centres. The efficacy was evaluated of the basis of reduction of upper respiratory tract infections (URIs) symptoms between the first and second visits with the application of the chi-square test. RESULTS: Results: The most common primary diagnoses for which AA was used were common colds and recurrent acute URIs of viral aetiology. Symptoms reduction or resolution were reported in over: 81% of children with sore throat and/or hoarseness, 72% of children with earache, 64% of children with nasal discharge and/or the feeling of congested nose, 63% of children with cough, 89% of children with fever and 82% of children with sleep disturbances. Improvement in appetite was achieved in more than 66% of children. Almost 60% of the paediatric patients or their carers included in the study group were very satisfied with the efficacy of AA. More than 66% of carers were very satisfied with the dosing regimen and the vast majority of them (99%) would recommend the preparation to others. Two children demonstrated adverse effects (diarrhoea, abdominal pain) that were induced by application of the studied product. They resolved after its discontinuation. CONCLUSION: Conclusions: AA applied in treatment of URIs in children highly effectively reduces symptoms of the diseases. Paediatric patients and their carers are satisfied with therapeutic effects of the syrup with regards to its all indications.

Cladophora glomerata enriched by biosorption with Mn(II) ions alleviates lipopolysaccharide-induced osteomyelitis-like model in MC3T3-E1, and 4B12 osteoclastogenesis.

Chronic osteomyelitis, a bone infectious disease, is characterized by dysregulation of bone homeostasis, which results in excessive bone resorption. Lipopolysaccharide (LPS) which is a gram-negative endotoxin was shown to inhibit osteoblast differentiation and to induce apoptosis and osteoclasts formation in vitro. While effective therapy against bacteria-induced bone destruction is quite limited, the investigation of potential drugs that restore down-regulated osteoblast function remains a major goal in the prevention of bone destruction in infective bone diseases. This investigation aimed to rescue LPS-induced MC3T3-E1 pre-osteoblastic cell line using the methanolic extract of Cladophora glomerata enriched with Mn(II) ions by biosorption. LPS-induced MC3T3-E1 cultures supplemented with C. glomerata methanolic extract were tested for expression of the main genes and microRNAs involved in the osteogenesis pathway using RT-PCR. Moreover, osteoclastogenesis of 4B12 cells was also investigated by tartrate-resistant acid phosphatase (TRAP) assay. Treatment with algal extract significantly restored LPS-suppressed bone mineralization and the mRNA expression levels of osteoblast-specific genes such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OCN), osteopontin (OPN), miR-27a and miR-29b. The extract also inhibited osteoblast apoptosis, significantly restored the down-regulated expression of Bcl-2, and decreased the loss of MMP and reactive oxygen spices (ROS) production in MC3T3-E1 cells induced by LPS. Furthermore, pre-treatment with algal extract strongly decreased the activation of osteoclast in MC3T3-E1-4B12 coculture system stimulated by LPS. Our findings suggest that C. glomerata enriched with Mn(II) ions may be a potential raw material for the development of drug for preventing abnormal bone loss induced by LPS in bacteria-induced bone osteomyelitis.

[ALLERGIC ALVEOLITIS [ARTICLE IN POLISH]].

Allergic alveolitis (AA) is a group of diseases with an immunologic background evoked by chronic antigen inhalation. The diagnosis is difficult due to the diversity and non-specific character of symptoms and different clinical severity. AA is the third most often interstitial-lung-disease, comprising 4-15% of all interstitial diseases. It's often related to professional exposure. Farmer's lung, a hypersensitivity pneumonitis is the most common AA. By binding precipitins to form immunologic complexes, antigens trigger an early phase acute reaction in the lung tissue thus initiating disease's progression. In the chronic phase endolobular fibrosis located in the upper lobes prevails. Disease differs in course depending the type and time of antigen exposition. Thus, avoiding antigen exposition is the first-line-therapy. Acute form is characterized by fever, chills, dyspnea, and cough. It usually starts 4-8 hours after intensive exposure. Early diagnosis leads to a good prognosis. When the exposition to the antigen stops, acute form of AA usually self-limits within 24-48 hours. Only in severe cases 0.5-1.0 mg/kg/d (up 60 mg/d) can be required for 1-2 weeks with a subsequent dose reduction. Long-term usually leads to chronic form with more serious deteriorations, including severe dyspnea and chronic cough (it takes months-years for them to develop, however). There is no effective therapy, in rapidly progressing cases 40-60 mg/g of prednisone repeated in 4-week-cycles can be recommended. Usually it does not stop the progression, and pulmonary fibrosis followed by respiratory insufficiency develop. Symptoms duration at diagnosis and effectiveness of antigen elimination are the known prognostic factors.

The role of psychological and medical variables in the process of adaptation to life with chronic illness in a group of COPD outpatients.

Many studies suggest that psychological factors play an important role in chronic diseases. This study aimed to describe the role of certain medical variables (airflow obstruction indicators), personal resources, coping strategies, and health-related quality of life (HRQoL) in the process of adaptation to chronic obstructive pulmonary disease (COPD). The Brief COPE inventory, the General Self-Efficacy Scale, COPD Assessment Test, and the Acceptance of Life with the Disease Scale were completed by 111 outpatients. Groups of patients distinguished based on degree of airflow obstruction did not differ in frequency of use of coping strategies, General Self-efficacy, HRQoL, or level of acceptance of life with the disease. Groups distinguished in terms of frequency of the strategies used differed in terms of indicators of airflow obstruction and acceptance of life with the disease. General Self-efficacy was correlated with active coping, use of emotional support, and planning. The best predictors of Acceptance of Life with the Disease were coping strategies, HRQoL, and General Self-efficacy. The obtained data indicated that psychological factors play an important role in adapting to life with illness. This study also found that self-efficacy is a very significant personal resource which future psychological interventions for COPD could focus on.

Cervical cancer - causes and prevention of hpv infections in the opinions of young polish women: a cross-sectional survey.

OBJECTIVE: Introduction: Cervical cancer is an important issue of gynecologic oncology. The awareness of this disease, the attitude towards HPV vaccination and cytological screening play an important role in decreasing morbidity and mortality due to cervical cancer. The aim: To assess the various aspects of knowledge regarding cervical cancer, risk factors for this disease, the role of HPV infection and the attitude to primary (vaccination) and secondary (cytological screening) prevention among young women. PATIENTS AND METHODS: Materials and methods: The study was performed using CAWI method based on original questionnaire in electronic form. Online completing of the survey was voluntary and anonymous. RESULTS: Results: The study was conducted in a group of 2058 women aged 19-33. In total 98.4% of respondents came across the term "cervical cancer", 84.1% knew that cervical cancer could be prevented and the following were identified as the main risk factors: cervical cancer in closest relatives (85.3%) and HPV infection (81.9%). Although according to 82.0% of women HPV infection can be prevented by vaccination, only 18.4% of respondents were vaccinated. The main reason for non-vaccination was lack of knowledge about the availability of the vaccine (41.2%) and high price (32.0%). Of the unvaccinated people, 63.5% declare their will to be vaccinated in the future. Concerning secondary prevention, 98.6% of the respondents admitted that they knew the term "cytological examination", 89.0% indicated that this examination detected the presence of pre-cancerous lesions, and according to 58.4% of respondents, this test should be performed after sexual initiation. Despite the fact that 80.5% of respondents confirmed the fact of beginning sexual activity (44.4% of them had more than 1 partner), 17.1% of the respondents admitted that they didn't go to gynecologist yet. Approximately 84% of respondents believe that the amount of information on cervical cancer prophylaxis and HPV infections currently providing is insufficient. CONCLUSION: Conclusions: The basic terms regarding primary (vaccination) and secondary (prophylactic tests) prevention of cervical cancer have been widely known. However, the knowledge about specific risk factors, sexual behaviors contributing to HPV infection and, consequently, the ability to self-identify as belonging to higher risk group is insufficient. It is justified to conduct educational activities regarding the assessment of risks related to cervical cancer addressed to young women. Together with education, HPV vaccination and secondary prevention programs require financial support.

Factors affecting the quality of life of chronic dialysis patients.

Background: Patients on hemodialysis must adjust their life plans to the treatment. They are aware of losing their health and independence. Therefore, acceptance of illness (AI) is important and allows the patient to adjust to new situation and alleviates negative emotions. Methods: The aim of study was to assess the impact of AI and other socioclinical variables on hemodialysis patients' quality of life (QoL). The study included 100 patients aged 20-85 (M = 57), treated with hemodialysis for at least 2 years. Two validated instruments were used: the Acceptance of Illness Scale (AIS) and the World Health Organization Quality of Life questionnaire. Results: High, moderate and low level of AI was found for 15, 61 and 24 patients, respectively. The QoL increased with the AI score. In physical domain, it reached 69.8 ± 12.4 in the high AIS group, 54.2 ± 15.3 in the moderate AIS group and 42.7 ± 12.3 in the low AIS group ( P < 0.001). The psychological domain scores were 70.3 ± 12.8, 57.2 ± 15.0 and 49.7 ± 11.8 ( P < 0.001), respectively. The environmental domain scores were 68.8 ± 13.3,59.0 ± 12.6 and 53.0 ± 11.6 ( P < 0.001), respectively. AIS scores were positively correlated with QoL in three domains: physical ( r = 0.549; P < 0.0001), psychological ( r = 0.505; P < 0.0001) and environmental ( r = 0.444; P < 0.0001). In multiple-factor analysis, AI was independent predictors in physical domains (ß = +0.210), psychological domain (ß = +0.402) and environmental domain (ß = +0.204). No correlation or predictive value was found for the social relationship domain, however. Conclusions: Patients on dialysis have moderate-to-low AI. AI is an independent predictor positively correlated with QoL in all domains except for social relationships. The social and psychological support for dialyzed patient might improve their HRQoL and illness acceptance.

efficacy of dry extract of ivy leaves in the treatment of productive cough.

OBJECTIVE: Introduction: Coughing is a physiological, spontaneous defense mechanism against irritants that stimulate respiratory mucosa. Productive cough should be not suppressed; instead, mucus-dissolving agents are recommended. One of the expectorants, which increases the excretion volume, is the herbal medicine derived from ivy leaves. The ivy extract contains triterpene saponins, which have secretory properties. The aim of this study was to determine the effectiveness and safety of the treatment with the medicinal product Hedussin®, containing dry ivy extract, in the therapy of productive cough in the course of the respiratory tract infection. PATIENTS AND METHODS: Material and methods:This was a non-randomized, non-interventional, multicenter, open-label, post-authorization effectiveness study (PAES). The study group consisted of 464 patients aged 2-12 years with productive cough. The study was supported by a questionnaire that included: the type of cough etiological factor, Bronchitis Severity Score (BSS), temperature, and prescription of antibiotic therapy. Effectiveness and safety of the therapy with Hedussin® was assessed at the follow-up visit. RESULTS: Results and conclusion: Improvement in cough was reported in 93.3% subjects; improvement in chest pain on coughing was reported in 84.7%, in wheezing - in 90.0%, in dyspnoea - in 88.7%, and in auscultation changes - in 94.8%. In addition, decline or normalization of body temperature was found in 96.0% of subjects. No adverse drug reactions were reported in the study population. The non-antibiotic treated group showed similar proportions. The results of this study support the efficacy of Hedussin® prescribed for the treatment of productive cough in the course of respiratory tract infections. Hedussin® was well tolerated by sick children aged 2-12 years.

Socioeconomic Effects of Chronic Obstructive Pulmonary Disease from the Public Payer's Perspective in Poland.

Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of death worldwide and the total number of people affected reaches over 200 million. It is estimated that approximately 50 % of persons having COPD are not aware of it. In the EU, it is estimated that the total annual costs of COPD exceed €140 billion, and the expected increase in the number of cases and deaths due to COPD would further enhance economic and social costs of the disease. In this article we present the results of cost analysis of health care benefits associated with the treatment of COPD and with the disease-related incapacity for work. The analysis is based on the data of the National Health Fund and the Social Insurance Institutions, public payers of health benefits in Poland. The annual 2012 expenditures incurred for COPD treatment was €40 million, and the benefits associated with incapacity for work reached more than €55 million. The extent of these expenditures indicates that it is necessary to optimize the functioning system, including the allocation of resources for prevention, social awareness, and detection of COPD at early stages when treatment costs are relatively low.

[Immunomodulatory role of Biostymina® and Bioaron® C in the prevention and treatment of upper respiratory tract infections]. / Immunomodulacyjna rola Biostyminy® i Bioaronu® C w profilaktyce i leczeniu infekcji górnych dróg oddechowych.

A properly functioning immune system among others protects the organism against the development of infections. In certain situations, its activity can be impaired, which can result in an increased risk of viral and bacterial infection development. An aqueous extract of aloe arborescens (Aloe arborescens Mill.) has been used as add-on therapy for many years due to its immunomodulatory effect resulting in increased anti-inflammatory, anti-viral and anti-bacterial activity. This effect is mainly due to lectins (glycoproteins) and mannans (polysaccharides). Over the past years products containing the aqueous extract of aloe arborescens have been subjected to numerous studies in vitro as well as pharmacological investigations and clinical-observational studies. Based on literature data as well as on the results of observational studies carried out in Poland, a positive immunomodulating effect of Aloe extract containing products has been demonstrated. This effect manifested in infection's symptoms amelioration and infection time shortening but also in general immune system stimulation resulting in less frequent infection recurrence. In Poland the only registered medicinal products containing aqueous extract of Aloe arborescens as an active substance, are Bioaron® C and Biostymina®. Both products showed good efficacy and safety profiles both in adults and in children.

[Treatment of cough in respiratory tract infections - the effect of combining the natural active compounds with thymol].

Cough is one of the characteristic symptoms of upper respiratory tract infections (URI). Herbal medicines are often used in the treatment of the cough associated with infection and to accelerate recovery or support the immune system. An example of such products are extracts of thyme and primrose, and also their combination with thymol. Thymus vulgaris is a spasmolytic, antimicrobial, anti-inflammatory, immunomodulatory and antioxidant agent. The most important component responsible for the activity of thyme is thymol contained in the volatile thyme oil. Primrose is, most of all, a saponine agent with expectorant and secretolytic activity, showing also spasmolytic, anti-inflammatory and antimicrobial effects. Because of the additive effects of the mentioned extracts and their wide activity profile they are often used as a combination drug. The use of this combination was assessed in the URI with the effects of alleviation of cough and dyspnea, and shortening the length of the disease. The effectiveness of the drug containing the extracts of thyme and primrose with the addition of thymol (Bronchosol®) was comparable to synthetic ambroxol and its safety has been proved. Moreover, the in-vitro antibacterial and antifungal effects of this drug have been evaluated.

Antiviral activity of the "Virus Blocking Factor" (VBF) derived i.a. from Pelargonium extract and Sambucus juice against different human-pathogenic cold viruses in vitro.

THE AIM: The in-vitro antiviral activity of the "Virus Blocking Factor" (VBF), a combination of Pelargonium extract and Sambucus juice with addition of Betaglucan 1,3 / 1,6, Zincum gluconium, Acidum ascorbicum, was studied against human pathogenic viruses: Influenza A H1N1 (FluA H1N1), Rhinovirus B subtype 14 (HRV14), Respiratory Syncytial Virus (RSV), Parainfluenzavirus subtype 3 (Para 3), and Adenovirus C subtype 5 (Adeno 5). METHOD: Antiviral activity was assessed using plaque-reduction assays after adding the test substance post infection of the MDCK, HeLa and HEp-2 cells with the viruses. Ribavirin Virazol and - in case of Adenovirus an internal laboratory standard - were used as positive controls. Cytotoxic effects of VBF and VBF Control onto the virus permissive MDCK, HeLa and HEp-2 cells were examined. Non-toxic concentrations of VBF were determined by the Methylthiazoletetrazolium test (MTT-Test). RESULTS AND CONCLUSIONS: In all antiviral studies VBF showed (2.1%) a dose-dependent antiviral activity against FluA H1N1 and HRV14 at non-toxic concentrations. A very strong effect was demonstrated in concentrations of 2.5% and 1.25% where replication of H1N1 and HRV14 was nearly completely blocked. Dose-dependent antiviral activity was detectable against RSV in a concentration range of 1.25% to 0.63% of the test item. Due to toxic side effects of a 2.5% concentration at least a "minor effect" of about 30% (1.25% solution) against Para 3 infected HEp-2 cells could be determined. Concerning Adeno 5 not any antiviral activity could be demonstrated in all studies with all tested substance concentrations of VBF. VBF Control did not show any cytotoxicity and antiviral effects. Further research is needed to elucidate clinical effect of VBF.

Antiviral activity of the "Virus Blocking Factor" (VBF) derived i.a. from Pelargonium extract and Sambucus juice against different human-pathogenic cold viruses in vitro.

THE AIM: The in-vitro antiviral activity of the "Virus Blocking Factor" (VBF), a combination of Pelargonium extract and Sambucus juice with addition of Betaglucan 1,3 / 1,6, Zincum gluconium, Acidum ascorbicum, was studied against human pathogenic viruses: Influenza A H1N1 (FluA H1N1), Rhinovirus B subtype 14 (HRV14), Respiratory Syncytial Virus (RSV), Parainfluenzavirus subtype 3 (Para 3), and Adenovirus C subtype 5 (Adeno 5). METHOD: Antiviral activity was assessed using plaque-reduction assays after adding the test substance post infection of the MDCK, HeLa and HEp-2 cells with the viruses. Ribavirin Virazol and - in case of Adenovirus an internal laboratory standard - were used as positive controls. Cytotoxic effects of VBF and VBF Control onto the virus permissive MDCK, HeLa and HEp-2 cells were examined. Non-toxic concentrations of VBF were determined by the Methylthiazoletetrazolium test (MTT-Test). RESULTS AND CONCLUSIONS: In all antiviral studies VBF showed (2.1%) a dose-dependent antiviral activity against FluA H1N1 and HRV14 at non-toxic concentrations. A very strong effect was demonstrated in concentrations of 2.5% and 1.25% where replication of H1N1 and HRV14 was nearly completely blocked. Dose-dependent antiviral activity was detectable against RSV in a concentration range of 1.25% to 0.63% of the test item. Due to toxic side effects of a 2.5% concentration at least a "minor effect" of about 30% (1.25% solution) against Para 3 infected HEp-2 cells could be determined. Concerning Adeno 5 not any antiviral activity could be demonstrated in all studies with all tested substance concentrations of VBF. VBF Control did not show any cytotoxicity and antiviral effects. Further research is needed to elucidate clinical effect of VBF.

[Efficacy and safety of acute bronchitis treatment in adults--a comparison of Bronchosol® syrup and synthetic preparations with ambroxol. Results of observational study]. / Skutecznosc i tolerancja syropu Bronchosol® w leczeniu ostrego zapalenia oskrzeli u doroslych. Porównanie z preparatami syntetycznymi zawierajacymi ambroksol--badanie obserwacyjne.

INTRODUCTION: Upper respiratory tract infections (URTI), including acute bronchitis, are the frequent health problems and the most common reason for acute cough in adults. Even though the infections are caused mainly by viruses, and their course is usually not complicated, febrifuges, i.a. mucokinetics, or antitussives are used in the treatment of URTI in order to improve the quality of life and safety of patients. THE AIM: To evaluate the efficacy and safety of Bronchosol® herbal syrup in comparison to ambroxol preparations in the treatment of acute bronchitis in adult patients. MATERIALS AND METHODS: The Bronchosol®/2013 study was a non-interventional, prospective, open-label, observational study. Data from adult patients treated with Bronchosol® syrup for acute bronchitis were collected and compared with data from patients treated for the same condition with ambroxol preparations. The severity of bronchitis symptoms was evaluated with the BSS (Bronchitis Severity Score) scale, and patients'quality of life wasassessed with the VAS (Visual Analogue Scale) scale. Between visits patients conducted self-observations and filled out observation diaries. Moreover, the data on adverse events were collected. RESULTS: In 87.68% of patients the infections were cured. Most of patients considered the studied drugs to be the agent decreasing the duration of infection and its intensity. The percentage of patients who declared that they had a less intense cough than during earlier infections was higher in the group of patients treated with Bronchosol® syrup in comparison to ambroxol treated patients (60.22% vs. 45.03%). 91.94% of patients treated with Bronchosol® considered this syrup to be very safe; in the ambroxol group such a declaration was made by 76.61% of patients. CONCLUSIONS: Bronchosol® syrup is an efficient, well-tolerated, and safe drug. Its efficacy in the treatment of acute bronchitis symptoms in adult patients is similar to the efficacy of ambroxol preparations.

The statement of the Polish Society of Allergology experts on the treatment of difficult-to-treat asthma.

The main objective of asthma treatment is to control symptoms of the disease; however, despite the availability of guidelines and many groups of medications, the degree of control of this condition is insufficient. In difficult-to-treat asthma, the optimal control cannot be achieved due to reasons independent of the disease. Factors worsening asthma control include: inadequate treatment plan (low therapy adherence and compliance), inappropriate inhalation technique, insufficient symptom control using the available classes of medications, incomplete response to treatment (non-responders, steroid-resistance), incorrect diagnosis of asthma or comorbidities, and environmental factors. In order to achieve the optimal asthma control, it is recommended to: take therapeutic decisions with the patient, assess the probability of non-compliance, perform detailed diagnostics and initiate treatment of concomitant diseases, carry out differential diagnosis of conditions mimicking asthma, educate the patient as to the inhalation technique and check it, eliminate unfavourable environmental factors, and modify current treatment. New treatment options for patients with asthma include: ultra-long-acting beta2-agonists, long-acting muscarine receptor antagonists (LAMA), monoclonal antibodies, and non-pharmacological interventions. The only LAMA approved for treatment of asthma is tiotropium bromide. The analyses performed demonstrated a high efficacy of tiotropium in terms of improved lung function parameters and prolonged time to the first asthma exacerbation. It is recommended as an add-on therapy at asthma treatment steps 4 and 5 according to GINA (Global Initiative for Asthma) 2014. The optimal asthma control is important from the medical as well as the economical point of view.

Climate warming, environmental degradation and pollution as drivers of antibiotic resistance.

Antibiotic resistance is a major challenge to public health, but human-caused environmental changes have not been widely recognized as its drivers. Here, we provide a comprehensive overview of the relationships between environmental degradation and antibiotic resistance, demonstrating that the former can potentially fuel the latter with significant public health outcomes. We describe that (i) global warming favors horizontal gene transfer, bacterial infections, the spread of drug-resistant pathogens due to water scarcity, and the release of resistance genes with wastewater; (ii) pesticide and metal pollution act as co-selectors of antibiotic resistance mechanisms; (iii) microplastics create conditions promoting and spreading antibiotic resistance and resistant bacteria; (iv) changes in land use, deforestation, and environmental pollution reduce microbial diversity, a natural barrier to antibiotic resistance spread. We argue that management of antibiotic resistance must integrate environmental goals, including mitigation of further increases in the Earth's surface temperature, better qualitative and quantitative protection of water resources, strengthening of sewage infrastructure and improving wastewater treatment, counteracting the microbial diversity loss, reduction of pesticide and metal emissions, and plastic use, and improving waste recycling. These actions should be accompanied by restricting antibiotic use only to clinically justified situations, developing novel treatments, and promoting prophylaxis. It is pivotal for health authorities and the medical community to adopt the protection of environmental quality as a part of public health measures, also in the context of antibiotic resistance management.

Prevalence of neurocognitive impairment in patients with rheumatoid arthritis - a systematic review and meta-analysis.

ObjectiveThis study aimed to evaluate prevalence rates (PRs) of neurocognitive impairment and its potential moderators among patients with rheumatoid arthritis (RA). MethodA systematic review of the available literature and data extraction was undertaken on 6 August 2021, with the update by 14 September 2023, by two reviewers independently. Literature was screened for reported rates of prevalence of neurocognitive impairment in RA patients. The meta-analysis was performed using RStudio with the "meta" library. ResultsTwenty-two studies that fulfilled all selection criteria were carefully analyzed. The PR of neurocognitive impairment was 0.49 [0.38-0.61] across all studies included in the review; 0.75 [0.54-0.88] for the MoCA; 0.56 [0.40-0.72] for the MMSE; and 0.26 [0.16-0.38] for comprehensive batteries. The meta-regression results indicated that, depending on the measurement method, the percentage of subjects with positive rheumatoid factor, women ratio, mean age of participants, mean duration of RA, and percentage of domains that had to be impaired to diagnose neurocognitive impairment turned out to be statistically significant moderators. ConclusionsNeurocognitive impairment is a clinically relevant condition in many RA patients, and its prevalence is alarming high.

Rheumatoid arthritis (RA) is a chronic systemic disease that has a significant negative impact on functioning. Difficulties experienced by RA patients described in the literature may involve various organs and systems, including the central nervous system. The results obtained in the review indicate that cognitive impairment may affect, depending on the measurement method, up to approximately 75% of the patients. Due to potential limitations related to cognitive dysfunctions, such as reduced compliance or difficulties in everyday functioning, such a high prevalence of neurocognitive dysfunctions is an argument for screening RA patients and developing appropriate support methods.

Cardiovascular Magnetic Resonance Imaging in Physically Fit Young Patients Sans Comorbidities Who Recently Recovered from Coronavirus Disease 2019 (COVID-19).

INTRODUCTION AND OBJECTIVE: Multiple studies showed that patients with a severe course of COVID-19 may develop cardiovascular complications. Assessment of the incidence of myocardial injury in young, physically fit male patients with no comorbidities, and asymptomatic/mild course of the disease who recovered from COVID-19. MATERIAL AND METHODS: A prospective, single-center, observational cohort study of 75 young (median[IQR] age 22 years) physically fit male patients, without comorbidities and smoking who recently recovered from COVID-19. Results were compared with a control group of age-matched, physically fit men with no comorbidities who tested negative for SARS-CoV-2. RESULTS: 19(25%) patients had possible COVID-19 related myocardial injury[PCRMI] on cardiovascular magnetic resonance [CMR] including definitive myocarditis (n=1;1.3%) and possible myocarditis (n=3;4%). Other abnormalities: mildly decreased (<50%) left ventricular(LV) ejection fraction (n=4;5%), increased LV end-diastolic volume index (n=8;11%) and LV mass index (n=9;12%). Patients with PCRMI had higher NT-pro-BNP level (29 vs 20pg/mL respectively, P=0.02) and lower LV ejection fraction (55% vs 59% respectively, P=0.03). PCRMI was demonstrated in 3(27%) volunteers from the control group based on the presence of LGE (2/18%) and decreased LV ejection fraction (1/9%). No volunteer from the control group was diagnosed with definitive or possible myocarditis. CONCLUSIONS: PCRMI was a frequent finding in young, asymptomatic, physically-fit patients sans comorbidities relatively late after recovery from COVID-19. Whereas no definitive or possible myocarditis was found in the control group, LGE was relatively frequent suggesting that our findings might not be COVID-19 specific. This warrants a need for further investigation into the long-term cardiovascular consequences of COVID-19.