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Objective: The objective of the study was to examine the impact of the COVID-19 pandemic on the work of medical personnel in terms of: task scope, preparation to perform medical tasks related to the pandemic, team collaboration, involvement in tasks performed, concerns about performing tasks related to the pandemic, stress levels., Methods: The mixed-method approach was applied to this cross-sectional study. The online questionnaire which included 40 questions was completed via Google among medical personnel in Poland. Eight semi-structured, in-depth interviews were conducted to deepen the data obtained with the questionnaires., Participants: The questionnaire was completed by 215 healthcare professionals, with the largest group being nurses (56.3%) followed by physicians (22.3%), midwives (11.6%) and other healthcare professionals (e.g., physiotherapists, paramedics, nutritionists - 9.8%). Among the respondents were people who worked in the hospital in the so-called "covid wards" (31.2%) and other hospital wards (60%) as well as people who were employed outside the hospital (8.8%)., Results: The pandemic affected the nature and range of tasks performed by health professionals. Initially, respondents felt unprepared to work under pandemic conditions, but over time their ratings increased in all areas studied. More than half of respondents reported no change in interpersonal relationship within the team, but nearly 35% noted a worsening and only one in 10 claimed improvement. Study participants rated their own commitment to tasks slightly higher than that of their colleagues (mean 4.9 and 4.4 respectively) but the overall rating was high. The mean self-rating of work stress increased from 3.7 before the pandemic to 5.1 during the pandemic. Most of the respondents were afraid of transmission of the infection to their relatives. Other fears included the possibility of making a medical error, not being able to help the patient, not having enough personal protective equipment (PPE) and contracting SARS-CoV-2., Conclusion: The conducted study revealed that the organization of medical care in the initial period of the pandemic, especially the hospital care of patients infected with SARS-CoV-2, was quite chaotic. The most affected were the people who were transferred to work in the covid wards. Not all medical professionals were prepared to work with the COVID-19 patients, as they lacked experience working in such facilities, especially in intensive care units (ICU). Working under time pressure and under new conditions led mainly to an increase in perceived stress and conflicts between staff., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Przyłęcki, Wieczorkowska, Pawlak-Kałuzińska, Cedrowska-Adamus and Gulczyńska.)

Objectives: Therapeutic hypothermia TH became broadly used in the management of the asphyxiated newborns. Although two cooling methods are used, so far the superiority of none of them has been established. The purpose of the study is to compare two cooling methods: selective head cooling (SHC) and whole body cooling (WBC) MATERIAL AND METHODS: We conducted a prospective observational study in newborns with HIE. The patients received one of methods: SHC or WBC. The eligibility criteria were similar to previous studies. Stability of cardio-respiratory parameters and short term outcomes were analyzed., Results: 78 neonates with hypoxic-ischemic encephalopathy due to perinatal asphyxia were involved in this study. The SHC group consisted of 51 newborns, the WBC group consisted of 27 patients. Both study groups had similar baseline characteristics and condition at birth. There were no significant differences in hospital course, neurological status and adverse effects associated with cooling procedure between groups. Analyzing the rate of thrombocytopenia and the number of transfusions of blood components no statistically significant differences were found between the groups., Conclusions: Results of our study indicate that two compared methods of TH despite varied target core temperature ranges do not differ significantly according to clinical course and risk of adverse events. Further observations are conducted and we look forward to the results of the long neurodevelopmental care.

The investigation of bronchoactive drugs in healthy volunteers may be divided into studies on the drug effects on basal airway calibre, the effects on induced bronchoconstriction and the examination of the pharmacokinetic and side effect profile of new chemical entities. In the studies presented in this paper, whole body plethysmography was used to assess the pharmacological activity of three new development compounds. In the first example, bronchodilatation was measured after administration of an anticholinergic drug. In two further examples, the bronchial effects were studied in asthma models in which an increase in airflow resistance was produced using inhaled methacholine and platelet activating factor (PAF). The method applied in these tests allowed the antagonistic effects of drugs on the constrictor effect of individual agents to be followed. Antiasthmatic drugs can also have a systemic effect on different physiological and biochemical parameters. These parameters can be applied as useful tools in the determination of the pharmacological activity of a given drug, irrespective of the conventional methods used to evaluate the efficacy of bronchodilators by the degree of bronchial muscular relaxation. A complex nonbronchial model is shown in order to demonstrate how it is possible to identify the pharmacologically effective dose of a new beta 2-adrenoceptor agonist.

The effects and tolerability of pramipexole, a new dopamine D2-receptor agonist, on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin levels were investigated in a randomized, double-blind, crossover study in 12 healthy volunteers. Single oral doses of 0.1, 0.2, and 0.3 mg pramipexole and placebo were studied over a period of 24 hours. Pramipexole decreased serum prolactin levels in a dose-dependent manner, with a maximum effect after 2 to 4 hours. Serum levels of human growth hormone were dose-dependently increased; however, this effect was only significant 2 hours after drug administration. Furthermore, a slight increase in serum cortisol levels and a slight decrease in serum thyrotropin levels was observed. Our findings show for the first time pharmacodynamic effects of pramipexole after single oral doses in healthy volunteers. The compound was well tolerated and showed an endocrine profile similar to other dopamine D2-agonists.

Platelet-activating factor (PAF) is a unique phospholipid mediator with multifunctional properties. Evidence generated in experimental studies suggests that PAF plays a pathogenetic role in anaphylactic, inflammatory and immunogenic reactions. Apafant (WEB 2086, CAS 105219-56-5), a novel synthetic PAF receptor antagonist, was administered to a total of 101 healthy volunteers within 5 studies to investigate its pharmacologic activity, pharmacokinetic behaviour and safety profile. Pharmacologic activity was monitored by inhibition of 5 x 10(-8) mol/l PAF-induced platelet aggregation ex vivo. The following treatment schedules were studied: oral single dose 1.25 to 400 mg; oral multiple dose 100 mg t.i.d. over 7 days; i.v. infusion 0.5 to 50 mg (over 30 min); inhalative administration up to 1.0 mg. PAF induced platelet aggregation was virtually completely inhibited by single oral doses of 20 mg upwards, throughout during the multiple oral dose study, at all dose levels tested in the i.v. study and (significantly but not completely) at 0.5 and 1.0 mg in the inhalative study. Following oral administrations (capsules) apafant is absorbed rapidly (tmax 1 to 2 h), there is linear pharmacokinetics for the mean plasma concentrations of apafant measured by RIA as well as for the areas under the curve (AUCs). Approximately 60% of apafant is bound to plasma protein, the mean volume of distribution is 28 l, about 44% of an oral dose is excreted in the urine, the mean renal clearance is 192 ml/min. No accumulation of the drug occurred in volunteers with normal kidney function. No clinically relevant drug related adverse events or changes in laboratory or vital parameters such as blood pressure, heart rate, respiratory rate and ECG were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

New H1-receptor antagonists are assessed not only for their H1 antihistaminic activity but also for their central nervous system (CNS) side effects. Fifteen healthy subjects received a once daily dose of 5 mg, 10 mg or 20 mg of epinastine, or a twice daily dose of 60 mg of terfenadine or placebo in a randomized double-blind (double-dummy) crossover study. The response to histamine-induced skin wheals was compared. CNS effects were evaluated by a multiple reaction time task, a finger tapping test and a self-rating scale (Bf-S von Zerssen) to assess mood state. Epinastine attenuated the wheal size in response to histamine in a dose-dependent manner. In addition, all epinastine dosages had a distinctly faster onset of action than terfenadine. All active treatments (5 mg, 10 mg, 20 mg epinastine and 60 mg terfenadine) attained their maximum effects 4 h after administration. At this time point and also 12 h after administration, 20 mg of epinastine were significantly more effective than 60 mg of terfenadine. Single 10 mg and 20 mg doses of epinastine were as effective as terfenadine given twice daily, and significantly more effective than placebo 24 h after drug administration (i.e. 12 h after the second dose of terfenadine). The psychometric tests for CNS effects did not reveal any difference among epinastine, terfenadine and placebo. In conclusion, epinastine is one of the most effective peripherally acting H1 antagonist which lacks significant CNS side effects and is suitable as a once daily dosage regimen.

Recent research on asthma mediators has concentrated more and more on platelet-activating factor (PAF), which is one of the most potent bronchoconstrictors known thus far. Inhalant PAF challenge in healthy volunteers may provide a mean of testing PAF antagonists. The usefulness of the PAF provocation test in measuring the pharmacologic activity of a new PAF antagonist, WEB-2086, has been examined in 12 healthy volunteers in a double-blind, placebo-controlled, within-subject crossover study. PAF-induced immediate bronchoconstriction, slight hemodynamic changes, and PAF-related subjective side effects. Premedication with WEB-2086 (40 mg) completely prevented any increase in airway resistance after PAF inhalation, as well as development of most of the cardiovascular and side effects induced by PAF. The clear protection against PAF-induced pharmacologic effects can be explained by the specific PAF-antagonistic activity of WEB-2086. The method described in this article may be applied as a useful tool for looking at PAF-antagonistic activity in healthy volunteers.

The inhibitory effects of 3-amino-9,13b-dihydro-1H-dibenz[1,5-a]azepine hydrochloride (WAL 801 CL), a new H1-receptor antagonist, on histamine-induced skin wheals were studied in 9 volunteers. The study was a double-blind, randomized (Latin square) change-over, intraindividual comparison of the effects of single doses of 2,6 and 18 mg WAL 801 CL and of placebo and 2 mg ketotifen on skin wheals induced by intradermal injections of 5 micrograms hystamine 1, 2, 4, 6 and 8 h after administration of the drugs. The injection of 5 micrograms was also made prior to each drug administration. The effects on psychological performance and the subjective state were also evaluated. The following tests were employed: simple visual reaction time (RT), critical flicker fusion frequency (C3F) and von Zerssen's self-rating scale Bf-S, assessing state of mood. There was a washout period of at least 72 h between each course of treatment. A decrease in the size of the histamine wheal was observed 1 h after WAL 801 CL and was maintained for at least 8 h. The reduction in the size of the histamine wheal was between 44% (2.0 mg) and 71% (18.0 mg). After ketotifen a marked decrease in the wheal area was observed between 4 and 8 h after administration of the drug, with maximum histamine antagonism of 59% after 6 h. The inhibitory effects of 6 and 18 mg WAL 801 CL and 2 mg ketotifen were statistically significant compared with placebo. 8 of 9 subjects felt tired (subjective report) after ketotifen, corresponding changes could be detected by Zerssen's state of mood scale Bf-S, but not by other psychological performance measures (RT, C3F).(ABSTRACT TRUNCATED AT 250 WORDS)

1, 4, 12 and 24 micrograms SOM 1397 CL, a new beta 2-adrenergic bronchodilator, were administered by inhalation to 10 healthy volunteers in a double-blind, placebo-controlled, within-subject crossover study in order to assess circulatory, tremorogenic and biochemical effects. 1 microgram SOM 1397 CL did not cause any relevant changes in the measured parameters. After administration of 4 micrograms a slight but continuous increase in tremor amplitude and c-AMP was observed. The effects on hemodynamics and other laboratory values could be considered negligible. Overdoses of 12 and 24 micrograms resulted in a dose-dependent increase in systolic blood pressure, pulse rate, tremor amplitude, alpha-AMP and lactic acid, as well as in a decrease of diastolic blood pressure and potassium. These effects may be partly attributable to beta 2-receptor stimulation. The method described in this paper can be applied as a useful tool for determination of beta 2-adrenergic activity in healthy volunteers, independent of the conventional methods which are used to evaluate efficacy of bronchodilators by the degree of bronchial muscular relaxation.

Provocation tests with acetylcholine, methacholine, histamine and carbachol are used as models for measuring bronchospasmolytics in patients with bronchial hyperreactivity. The possibilities of the methacholine provocation test for the measurement of bronchospasmolytic agents in healthy volunteers have been examined. The relevance of this method will be shown by the example of the effects of two beta 2-mimetics in comparison to placebo. Under placebo conditions, methacholine provocation resulted in an increase of bronchial resistance of approximately 200% in volunteers. The various dosages of the two test substances showed a clear, dose-related bronchospasmolysis. The described method can be used as a model of investigation for testing bronchospasmolytics in healthy volunteers.

WEB 2086 is a novel PAF-acether antagonist, whose pharmacological action in man has only been preliminarily defined. Twelve healthy male volunteers received oral doses of 5, 30 and 90 mg and over the following 24 h inhibition of 5 x 10(-8) M PAF-acether-induced platelet aggregation ex vivo was studied as an indicator of pharmacological activity. WEB 2086 inhibited PAF-acether-induced platelet aggregation in all the doses tested, with the maximum effect 1 to 2 h after administration. After 2 h 5- 30- and 90-mg doses caused, respectively, 87, 98 and 100% inhibition. The magnitude and duration of the inhibitory effect was dose-dependent, with a significant action still detectable 10 h after administration of all three doses, and 12 h after administration of the two highest doses (30 and 90 mg). The subjects did not complain of any significant adverse effect and all completed the study.

Platelet aggregation induced ex vivo by aggregating factors such as adrenaline, ADP, collagen or PAF may be useful as a model for describing drug effects in humans. In the two studies reported here, PAF-induced platelet aggregation ex vivo was used as an indicator of the pharmacological activity in healthy volunteers of the newly developed specific PAF-antagonist WEB 2086. In intravenous and inhalative single rising dose tolerance trials this method proved useful for monitoring the pharmacological action of the compound tested. After administration of placebo no relevant pharmacological activity was observed. In both studies increasing dosages of the test substance showed clear, dose-related inhibition of PAF-induced platelet aggregation. Ex vivo PAF-induced platelet aggregation thus provides a simple and rapid means of assessing functional PAF antagonism during trials of PAF-antagonists in human volunteers.