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Réka Bodnár,1,2 Ágnes Mészáros,2 Máté Oláh,2 Tamás Ágh3 1Department of Pediatric Pulmonology, Heim Pál Children’s Hospital, Budapest, Hungary; 2University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary; 3Syreon Research Institute, Budapest, Hungary Background: Inhaled antibiotics (ABs) are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF). The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF. Methods: A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality. Results: The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3), proportion of adherent patients (>75%–80% of required doses taken) ranged from 86% to 97%; in prospective cohort studies (n=3), adherence rates ranged between 36% and 92%, and in retrospective studies (n=4) it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste), and patient satisfaction. Conclusion: The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies) and the lack of a commonly accepted consensus on the definition of adherence in the reviewed articles. Routine adherence monitoring during CF care, discussing the possible reasons of suboptimal adherence with the patient, and changing treatment regimens on the basis of patient burden can individualize CF therapy for patients and may improve the level of adherence. Keywords: cystic fibrosis, antibiotics, adherence, compliance, Pseudomonas aeruginosa

The objective of this research is to assess the effect that extreme hydrologic events have on the propagation of sediment pulses in river corridors. These sediment-flow hazards are associated with large amounts of loose material suddenly deposited in rivers by the action of external factors or processes of natural or anthropogenic origin, including landslides, debris flows from tributaries, dam removal projects, and mining-related activities. Their occurrence is associated with severe channel aggradation and degradation, floodplain deposition, damage of infrastructure, and impairment of riparian and aquatic ecosystems. Given that the intensity of rainfall events have been significantly enhanced due to the influence of various human activities, sediment pulses are expected to become more common, with a more pronounced downstream impact as such climatic changes directly affect the magnitude, duration, and frequency of flows in riverine environments. Herein, numerical simulations were performed to characterize the propagation of a fine-grained sediment pulse for the 10-, 100-, and 500-yr storms. Results indicate that magnitude, frequency, and duration of the storms primarily influence the temporal variation of the total sediment discharge. In particular, these storm characteristics have a marked impact on the relationship between pre- and post-pulse conditions in the river channel, the dissipation of the pulse peak discharge, and the travel time of the pulse apex.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke. It is a critical condition that often leads to severe visual loss or blindness and can be a harbinger of further cerebrovascular events. Due to the lack of scientific data, there are no effective evidence-based forms of therapy for this condition. None of the conservative therapies have proven effective. The results of some previously published studies suggest a benefit of intravenous thrombolytic therapy in the same regimen as in the treatment of ischemic stroke. This work aims to present an overview of published clinical studies focused on the use of intravenous thrombolysis for CRAO, evaluate its efficacy and safety, and propose an optimal diagnostic and therapeutic algorithm for acute management of CRAO. Summary statistics of patient data from relevant studies indicate that a significant visual acuity improvement was achieved by a total of 45 % of patients receiving alteplase within 4.5 hours of symptoms onset. The occurrence of adverse events in this time window was not significant. Intravenous thrombolytic therapy in CRAO thus appears to be effective and safe. However, we still lack data from adequate prospective randomized controlled trials to confirm this conclusion. To date, two randomized trials are being conducted. The intravenous thrombolysis administration, patient monitoring, etiologic workup, and setting of effective secondary prevention should be ensured at the centre of highly specialized cerebrovascular care. Urgent transport of the CRAO patient to the nearest centre is essential.

Background: In the management of chronic diseases, treatment approaches have changed in recent decades. Not only are clinical outcomes assessed but also the patients' perception of their quality of life has become an important aspect., Objectives: The aim of our study was to compare the health-related quality of life (HRQoL) of children with cystic fibrosis (CF) to the HRQoL of asthmatic patients, to assess the level of agreement between parent proxy-report and child self-report and to measure the relationship between spirometry and HRQoL., Material and Methods: 172 children (mean age: 11.61±2.56 years) and their parents completed the questionnaire. The Hungarian version of the Pediatric Quality of Life InventoryTM 4.0 (PedsQLTM 4.0) Generic Core Scale was used to assess HRQoL. Lung function was assessed via spirometry., Results: Significantly lower PedsQLTM scores were measured for CF patients on the psychosocial health (p<0.05), emotional functioning (p<0.005) and school functioning (p<0.01) subscales and the total scale (p<0.05) from the children's self-report. The level of child-parent agreement was fair and moderate in both patient populations [intra-class correlation coefficient range (ICC) asthma=0.29-0.37; ICCCF=0.39-0.59, p<0.001]. The relationship between forced expiratory volume in 1 second (FEV1) and the physical health subscale (r=0.49, p<0.01) was moderate in young (8-12 years) children and also teenagers (13-18 years), with CF (r=0.58, p<0.05) from self-report. We found weak, non-significant correlations between FEV1 and PedsQLTM subscales in children with asthma (8-12 years) (r=-0.01-0.18, ns.)., Conclusions: Children suffering from CF perceive their HRQoL as poorer than children with asthma. In asthmatic patients, it is not sufficient to evaluate clinical outcomes (FEV1); subjective HRQoL should be also estimated in the course of patient care.

Introduction: Cystic fibrosis is a progressive multisystemic disease which affects the quality of life of patients., Aim: The aim of the study was to evaluate quality of life in Hungarian patients with cystic fibrosis., Methods: Validated Hungarian translation of The Cystic Fibrosis Questionnaire - Revised was used to measure quality of life. Clinical severity was determined on the basis of Shwachman-Kulczycki score. Lung function was measured using spirometry., Results: 59 patients were included from five centres in Hungary. The relationships between 8-13 year-old children self-report and parent proxy report was 0.77 (p<0.001) in physical functioning, 0.07 (p<0.001) in emotional functioning, 0.51 (p<0.001) in eating, 0.21 (p<0.001) in treatment burden, 0.54 (p<0.001) in body image, 0.49 (p<0.001) in respiratory symptoms and 0.40 (p<0.001) in digestive symptoms domains., Conclusions: In contrast to physical domains weak correlations were observed between answers obtained from children and their parents in psychosocial domains. The perception of both patients and their parents should be assessed when measuring quality of life in paediatric patients with cystic fibrosis.

Incidence and prevalence of tuberculosis (TB) shows a decreasing tendency in Hungary. The medical care of these patients represents a substantial cost to the health services. We assessed the direct costs of paediatric patients with TB in a Hungarian hospital. Patients participating in the study were 9 children, with an average age of 11.17 +/- 6.34 years. In the study group there were two immigrant patients (22, 23%), two (22, 23%) had multidrug-resistant TB (MDR-TB), five patients (62.5%) were contacts, six (66, 67%) had extrapulmonary tuberculosis and three (33, 34% suffered from other co-morbidities. The average direct cost of pulmonary TB was 2920 Euros, direct cost of MDR-TB was between 7300-9120 Euros. MDR-TB increases one and half times the period spent in hospital, two and half times the cost of inpatient care. Extrapulmonary TB with concomitant disease causes 3-7 times higher expenditures to the health service. According to our results we found significant differences between the cost of actual therapy and resources available; thus the compensation needs to be solved.

The monetary value of the unit averted collective dose at an individual reference dose (as alpha(base)-value) and the aversion against the high individual exposure were assessed by the WTP (Willingness To Pay) method. The original questionnaire and methodology were developed by the CEPN, France, for specialists in the nuclear field. Modifications to the questionnaire were introduced in 2000 to take into account the Hungarian aspects. In 2001, the questionnaire was further modified for use with the public in Hungary. The present paper refers to the results from the most recent studies on public exposure. The questionnaire was provided to 118 persons living in four different regions of Hungary, one near the U-mining site, one near a nuclear power plant, and two others far away from nuclear affected sites. Conversion of the questionnaire to be understandable by the public involved intensive modifications both in form and content. Only 83 to 86 respondents provided usable answers to questions related to the monetary value of the averted dose and the aversion coefficient. The alpha(base)-value was determined from the statistical value of life assessed by the willingness to pay of the respondents for the risk of fatal cancer averted. The mathematical form used to assess the aversion coefficient was a power function with respect to the individual dose, as already introduced in our earlier papers. The advantage of the power function is that the aversion coefficient is independent of the individual reference dose. According to the current results, the mean value of the lognormally distributed alpha-value at the individual reference dose (alpha(base)) takes 10,000 US dollars (person Sv)(-1) with large confidence bounds. The alpha(base)-value is about 50% higher than the alpha(base)-value estimated among the radiation specialists in Hungary, but 5-10 times less than the values obtained in highly developed countries like in France. The normally distributed aversion coefficient for the public assessed to 2.51 +/- 0.56 and is 30% higher than the value obtained by the Hungarian specialists in the nuclear field. Due to the high sensitivity of the alpha-value to the variation of individual reference dose (d0) the derivation of a generic d0-value will depend upon the circumstances of optimization.