CRUSE® -An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE® , the Chronic Urticaria Self Evaluation app, aims to address this unmet need. METHODS: CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations. RESULTS: CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days. CONCLUSIONS: The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.

Azithromycin with scaling and root planing versus scaling and root planing alone in the treatment of periodontitis: A randomized controlled trial.

Background: The growing interest in the possibilities of macrophages modulation with therapeutic purposes promotes new approaches for periodontitis treatment. Aim: The aim of this randomized controlled open clinical study was to evaluate the early clinical and immunological effects of the long-course azithromycin as an adjunct to scaling and root planing in periodontitis. Methods: 50 patients (with stage I-III, grade A/B periodontitis) and 22 periodontally healthy volunteers as the reference group were recruited. Following scaling and root planing (SRP), the patients were randomly assigned to one of two treatment modalities: SRP only (n = 25) and adjunct azithromycin (Az) treatment (n = 25). The patients were monitored at baseline, and 30 ± 5 days after therapy. Clinical attachment loss (CAL), periodontal probing depth (PPD) and bleeding on probing (BoP) were evaluated. Secondary outcome measures included mean changes in single-positive CD68 + and CD163 + macrophages (Mφs) density and ratio, evaluated by immunohistochemistry, and IL1-ß, IL-6, IL-10, TGF-ß levels, detected by ELISA. Results: At 1 month both groups showed significant improvements of CAL, PPD and BoP, without significant added benefit in terms of CAL, PPD and BoP of Az. But Az increased the density of CD68 + and CD163 + Mφs (P < 0.0001), decreased the CD68+/CD163 + ratio (P = 0.043), decreased IL-1ß (P < 0.01), IL-6 (P < 0.001) levels, and increased IL-10 (P < 0.0001) and TGF-ß (P < 0.001) levels compared to SRP and periodontitis at baseline. Conclusion: The long course of Az demonstrated modulation of CD68 + and CD163 + Mφs towards M2 polarization, which may play a significant role in achieving favorable long-term treatment outcomes. ClinicalTrials.gov.

Macrophage migration inhibitory factor receptor CD74 expression is associated with expansion and differentiation of effector T cells in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.

Prophylaxis of decidual CD68+/CD163+ macrophage disbalance in extracorporeal fertilized women.

The demographic crisis that prevailed in Ukraine in recent years, the state of war as a result of the aggression of the Russian Federation, reproductive losses among women of childbearing age are one of the most urgent problems in modern obstetrics and gynecology. One of the most effective methods of correcting impaired reproductive function is in vitro fertilization. The purpose of this work: is to develop a pharmacological complex for the prevention of imbalance of CD68+/CD163+ decidual macrophages in vitro fertilized women. Materials and methods: 105 pregnant women who were divided into 3 groups took part in the study. The first group included 20 women whose pregnancy occurred and is proceeding physiologically. The second group consisted of 85 women who became pregnant as a result of in vitro fertilization, including 37 pregnant women who refused prophylactic correction of the threat of premature birth, and 48 pregnant women who received prophylactic correction of the threat of premature birth: complex prescription of vitamin D3 2000 IU orally 2 times a day, micronized progesterone 200 mg 2 times a day and l-arginine aspartate 1000 mg 4 times a day, starting from 18 to 20 weeks of pregnancy. Results: In women who refused prophylactic correction of the threat of premature birth, a local increase in the activity of inducible NO-synthase and concentration of tumor necrosis factor-α, and a decrease in the activity of arginase and in the level of interleukin-10 were observed in the cervical mucus. They have a lower expression of CD163+ on placental decidual macrophages and an increased expression of CD68+, which indicates a shift in the polarization of macrophages from an anti-inflammatory to a pro-inflammatory phenotype. The use of prophylactic treatment brings the studied parameters closer to the results of women in whom pregnancy occurred physiologically. Conclusions: In women who became pregnant as a result of in vitro fertilization, at 28-30 weeks of pregnancy, changes specific for pro-inflammatory phenotype of decidual macrophages were observed. Complex administration of vitamin D3, micronized progesterone and l-arginine aspartate lead to restoration of anti-inflammatory phenotype of decidual macrophages.

PPARG stimulation restored lung mRNA expression of core clock, inflammation- and metabolism-related genes disrupted by reversed feeding in male mice.

The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating rhythm. Peroxisome proliferator-activated receptor gamma (PPARG) is a key molecule involved in circadian rhythm regulation, lung functions, and metabolic processes. We described the effect of the PPARG agonist pioglitazone (PZ) on the diurnal mRNA expression profile of core circadian clock genes (Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, and Per2) and metabolism- and inflammation-related genes (Nfe2l2, Pparg, Rela, and Cxcl5) in the male murine lung disrupted by reversed feeding (RF). In mice, RF disrupted the diurnal expression pattern of core clock genes. It decreased Nfe2l2 and Pparg and increased Rela and Cxcl5 expression in lung tissue. There were elevated levels of IL-6, TNF-alpha, total cells, macrophages, and lymphocyte counts in bronchoalveolar lavage (BAL) with a significant increase in vascular congestion and cellular infiltrates in male mouse lung tissue. Administration of PZ regained the diurnal clock gene expression, increased Nfe2l2 and Pparg expression, and reduced Rela, Cxcl5 expression and IL-6, TNF-alpha, and cellularity in BAL. PZ administration at 7 p.m. was more efficient than at 7 a.m.

UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

Metabolic, Apoptotic and Fibro-Inflammatory Profiles of the Heart Exposed to Environmental Electromagnetic Fields.

Environmental stress can disturb the integrative functioning of the cardiovascular system and trigger a number of adaptive and/or maladaptive cell responses. Concomitant with the expanding use of mobile communication systems, public exposure to electromagnetic fields (EMFs) raises the question of the impact of 900 MHz EMFs on cardiovascular health. Therefore, in this study, we experimentally investigated whether 915 MHz EMF exposure influenced cardiac metabolic, antioxidant, apoptotic, and fibro-inflammatory profiles in a mouse model. Healthy mice were sham-exposed or exposed to EMF for 14 days. Western blot analysis using whole cardiac tissue lysates demonstrated that there was no significant change in the expression of oxidative phosphorylation (OXPHOS) complexes between the control and EMF-exposed mice. In addition, the myocardial expression of fibro-inflammatory cytokines, antioxidant enzymes, and apoptosis-related markers remained unchanged in the EMF-challenged hearts. Finally, the structural integrity of the cardiac tissues was preserved among the groups. These findings suggest that the apoptotic, antioxidant, metabolic, and fibro-inflammatory profiles of the heart remained stable under conditions of EMF exposure in the analyzed mice.

Expression of periferal core molecular clock genes in oral mucosa depends on the chronotype in patients with maxillofacial cellulitis.

Introduction: Accurate determination of the patient's chronotype is one of the problems of personalized medicine. Recent studies have shown that determining of the expression of timing genes is a valuable method that can help gain molecular insight into a patient's intrinsic circadian timing. Odontogenic cellulitis is very common pathology. Since acute inflammatory diseases are an urgent pathology, the time of surgical intervention can correspond depend on the time of the patient's hospitalization. Materials and methods: The level of mRNA expression of peripheral circadian clock genes clock and bmal1, per1, cry1 in buccal epithelial cells in patients with odontogenic purulent inflammatory diseases of maxillofacial area in the morning and evening was investigated. Results: During analyzing the results of the mRNA expression study of the genes of the negative regulatory link of the peripheral molecular clock, per1 and cry1, in patients with Cellulitis of the maxillofacial area, a significant decrease (P = 0.0003) in the mRNA expression level of the cry1 gene by 2.61 times in the evening compared to its morning mRNA expression values. Conclusion: The obtained data indicate that in patients with odontogenic purulent inflammatory diseases of the maxillofacial area with an evening chronotype, a violation of the expression profile of the per1 gene in the cells of the buccal epithelium is noted, which is manifested by an increase in its evening expression in comparison with patients with a morning chronotype.

Polymorphism of tmprss2 (rs12329760) and severity of COVID-19 in the Ukrainian population: Response.

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Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.

BACKGROUND AND AIM: Angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 and serine 11A proteases (TMPRSS2, TMPRSS11A), and a cell surface cluster of differentiation 147 (CD147) might be a gene candidate that exerts the susceptibility to and mortality from coronavirus disease 19 (COVID-19). The aim of this study was to investigate the associations between ace2, tmprss2, tmprss11a, and cd147 polymorphic variants and the severity of COVID-19 in the Ukrainian population. METHODS: The study population consisted of the Ukrainian population with COVID-19: patients without oxygen therapy (n=62), with non-invasive (n=92) and invasive (n=35) oxygen therapy, as well as control subjects (n=92). Allelic polymorphisms of ace2 rs4240157, tmprss2 rs12329760, and tmprss11a rs353163 were determined by real-time PCR, and cd147 rs8259 polymorphism was detected by PCR with subsequent restrictase analysis. We compared investigated polymorphisms distribution with other populations by meta-analysis. RESULTS: Our study is the first to obtain data about the distribution of investigated gene polymorphisms in the Ukrainian population: tmprss2 rs12329760 - CC 60.9%, CT 35.9%, TT 3.2%; tmprss11a rs353163 - CC 46.7%, CT 40.2%, TT 13.1%; ace2 rs4240157 - CC 7.6%, C 18.5%, CT 22.8%, TT 19.6%, T 31.5%; cd147 rs8259 - TT 60.9%, AT 32.6%, AA 6.5%. This distribution was similar to the Northern, Western and Southern European populations. There was a statistically significant difference in the frequency of tmprss2 polymorphic genotypes CC 57.1%, CT 28.6%, and TT 14.3% (P<0.05) in COVID-19 patients with invasive oxygen therapy in comparison with non-invasive oxygen therapy. This tmprss2 mutation occurs in the scavenger receptor cysteine-rich (SRCR) domain and might be important for protein-protein interaction in a calcium-dependent manner. CONCLUSIONS: Our study indicated the presence of an association between the tmprss2 rs12329760 polymorphism and the severity of COVID-19 in the Ukrainian population.

Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study.

INTRODUCTION: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. METHODS: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. RESULTS: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. CONCLUSIONS: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Cutoff Values of MASK-air Patient-Reported Outcome Measures.

BACKGROUND: In clinical and epidemiological studies, cutoffs of patient-reported outcome measures can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cutoffs in MASK-air have not been tested. OBJECTIVE: To calculate cutoffs for VAS global, nasal, ocular, and asthma symptoms. METHODS: In a cross-sectional study design of all MASK-air participants, we compared (1) approaches based on the percentiles (tertiles or quartiles) of VAS distributions and (2) data-driven approaches based on clusters of data from 2 comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air real-world cross-sectional and longitudinal data to assess the most relevant cutoffs. RESULTS: We assessed 395,223 days from 23,201 MASK-air users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cutoff values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cutoff differentiating "controlled" and "partly-controlled" patients was similar to the cutoff value that had been arbitrarily used (20/100). However, a lower cutoff was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 vs the arbitrarily-used value of 50/100). CONCLUSIONS: Using a data-driven approach, we were able to define cutoff values for MASK-air VASs on allergy and asthma symptoms. This may allow for a better classification of patients with rhinitis and asthma according to different levels of control, supporting improved disease management.

PPARG agonist pioglitazone influences diurnal kidney medulla mRNA expression of core clock, inflammation-, and metabolism-related genes disrupted by reverse feeding in mice.

This study examined the influence of PPARG activation by pioglitazone (PG) on the mRNA of core clock, inflammation- and metabolism-related genes in the mouse kidney medulla as well as urinary sodium/potassium excretion rhythms disrupted by reverse feeding. Mice were assigned to daytime feeding and nighttime feeding groups. PG 20 mg/kg was administered at 7 am or 7 pm. On day 8 of the feeding intervention, mice were killed at noon and midnight. Kidney medulla expression of Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, Per2, Nfe2l2, Pparg, and Scnn1g was determined by qRT PCR. We measured urinary K+ , Na+ , urine volume, food, and H2 O intake. The reverse feeding uncoupled the peripheral clock gene rhythm in mouse kidney tissues. It was accompanied by a decreased expression of Nfe2l2 and Pparg as well as an increased expression of Rela and Scnn1g. These changes in gene expressions concurred with an increase in urinary Na+ , K+ , water excretion, microcirculation disorders, and cell loss, especially in distal tubules. PG induced the restoration of diurnal core clock gene expression as well as Nfe2l2, Pparg, Scnn1g mRNA, and decreased Rela expressions, stimulating Na+ reabsorption and inhibiting K+ excretion. PG intake at 7 pm was more effective than at 7 am.

Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities.

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Influence of age, gender characteristics, chronotype on the expression of core clock genes Per1, Clock, Bmal1 and Cry1 in buccal epithelium.

The purpose of the study is to determine the expression of the core clock genes in buccal epithelial cells of healthy people with different chronotypes. MATERIALS AND METHODS: Fourteen healthy volunteers with a healthy periodontium and oral mucosa (7 women and 7 men) were selected for participation in the trial. The buccal epithelium sampling was performed at 07:00 am and 07:00 pm in one day by cytological brush. The surveyed patients were examined chronotypically using the Horn-Ostberg test. The determination of the mRNA expression of the Per1, Clock, Bmal1, Cry1 genes was performed by quantitative real-time PCR. Statistical analysis was performed using two-way analysis of variance followed by Bonferroni post hoc tests. RESULTS: Per1 expression was higher in the morning, regardless of chronotype, age, and gender. The expression of the Clock demonstrated the prevalence of the evening in both chronotypes, in both men and women. Bmal1 was better expressed in the evening, regardless of age, gender, and chronotype. The expression of Cry1 did not show statistically significant differences between the indicators. CONCLUSIONS: The evening expression of Clock was higher in people with the evening chronotype than in people with the morning chronotype. The chronotype did not show any effect on the expression of Per1, Bmal1, and Cry1. Age and sex did not show any effect on the expression of the core clock genes.

The human toll and humanitarian crisis of the Russia-Ukraine war: the first 162 days.

BACKGROUND: We examined the human toll and subsequent humanitarian crisis resulting from the Russian invasion of Ukraine, which began on 24 February 2022. METHOD: We extracted and analysed data resulting from Russian military attacks on Ukrainians between 24 February and 4 August 2022. The data tracked direct deaths and injuries, damage to healthcare infrastructure and the impact on health, the destruction of residences, infrastructure, communication systems, and utility services - all of which disrupted the lives of Ukrainians. RESULTS: As of 4 August 2022, 5552 civilians were killed outright and 8513 injured in Ukraine as a result of Russian attacks. Local officials estimate as many as 24 328 people were also killed in mass atrocities, with Mariupol being the largest (n=22 000) such example. Aside from wide swaths of homes, schools, roads, and bridges destroyed, hospitals and health facilities from 21 cities across Ukraine came under attack. The disruption to water, gas, electricity, and internet services also extended to affect supplies of medications and other supplies owing to destroyed facilities or production that ceased due to the war. The data also show that Ukraine saw an increase in cases of HIV/AIDS, tuberculosis, and Coronavirus (COVID-19). CONCLUSIONS: The 2022 Russia-Ukraine War not only resulted in deaths and injuries but also impacted the lives and safety of Ukrainians through destruction of healthcare facilities and disrupted delivery of healthcare and supplies. The war is an ongoing humanitarian crisis given the continuing destruction of infrastructure and services that directly impact the well-being of human lives. The devastation, trauma and human cost of war will impact generations of Ukrainians to come.

The Allergic Rhinitis and Its Impact on Asthma (ARIA) Approach of Value-Added Medicines: As-Needed Treatment in Allergic Rhinitis.

Drug repurposing is a major field of value-added medicine. It involves investigating and evaluating existing drugs for new therapeutic purposes that address unmet healthcare needs. Several unmet needs in allergic rhinitis could be improved by drug repurposing. This could be game-changing for disease management. Current medications for allergic rhinitis are centered on continuous long-term treatment, and medication registration is based on randomized controlled trials carried out for a minimum of 14 days with adherence of 70% or greater. A new way of treating allergic rhinitis is to propose as-needed treatment depending on symptoms, rather than classical continuous treatment. This rostrum will discuss existing clinical trials on as-needed treatment for allergic rhinitis and real-world data obtained by the mobile health app MASK-air, which focuses on digitally-enabled, patient-centered care pathways.

Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference.

BACKGROUND: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. METHODS: We assessed the MASK-air® app data (May 2015-December 2020) by users self-reporting AR (16-90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. RESULTS: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71-0.80). CONCLUSION: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.

Etiology and efficacy of anti-microbial treatment for community-acquired pneumonia in adults requiring hospital admission in Ukraine.

BACKGROUND AND AIM: Empiric therapy of community-acquired pneumonia (CAP) remains the standard care and guidelines are mostly based on published data from the United States or Europe. In this study, we determined the bacterial etiology of CAP and evaluated the clinical outcomes under antimicrobial treatment of CAP in Ukraine. METHODS: A total of 98 adult subjects with CAP and PORT risk II-IV were recruited for the study. The sputum diagnostic samples were obtained from all patients for causative pathogen identification. Subjects were randomly assigned in a 1:1 ratio to receive delafloxacin 300 mg (n=51) or moxifloxacin 400 mg (n=47) with blinding placebo. The switch to oral treatment was after a minimum of 6 IV doses according to clinical criteria. The total duration of antibacterial treatment was 5-10 days. In vitro susceptibility of pathogens to delafloxacin and other comparator antibiotics was determined. RESULTS: The most frequently isolated pathogens in adults with CAP were S. pneumoniae - 19.5%, M. pneumoniae - 15.3%, H. influenzae - 13.2%, S. aureus - 10.5%, K. pneumoniae - 10.1%, and H. parainfluenzae - 6.4%. All isolates of S. pneumoniae, S. aureus, M. pneumoniae had sufficient susceptibility to appropriate antibiotics. 9.0% of H. influenzae strains were susceptible to azithromycin. 94.8 % of patients had a successful clinical response to delafloxacin at the end of treatment and 93.9 % - at test-of-cure. CONCLUSIONS: In Ukraine, the major bacterial agents that induced CAP in adults were S. pneumoniae, M. pneumoniae, H. influenzae, S. aureus, K. pneumoniae, H. parainfluenzae, E. cloacae, L. pneumophila. Delafloxacin is a promising effective antibiotic for monotherapy for CAP in adults and could be used in cases of antimicrobial-resistant strains.

Allergen immunotherapy in MASK-air users in real-life: Results of a Bayesian mixed-effects model.

BACKGROUND: Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. OBJECTIVE: To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. METHODS: We assessed the MASK-air® data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. RESULTS: We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = -12.1;-2.8), lower VAS Work (average difference = 5.0; 95%CrI = -8.5;-1.5), and a lower CSMS (average difference = 3.7; 95%CrI = -9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = -17.2;-2.8), lower VAS Work (average difference = 7.8; 95%CrI = -15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = -18.5;0.2). CONCLUSION: In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its 'real-world' effectiveness.