Pharmacovigilance and Adverse Drug Reaction Reporting among the General Public in Lithuania: A Cross-Sectional Study.

Background: Despite the fact that for over ten years, Lithuanian consumers have been able to report adverse drug reactions (ADR) directly to the competent authority, reporting rates remain low. A comprehensive understanding of consumer perceptions and experiences regarding ADRs is needed to ascertain further factors impacting their engagement in ADR reporting. This study aimed to assess consumer knowledge of, attitude toward, and practice of reporting ADRs. Methods: A questionnaire-guided cross-sectional survey among 404 consumers between October 2021 and June 2022 was conducted. The semi-structured questionnaire comprised open-ended and closed-ended questions to explore the sociodemographic characteristics and general knowledge of ADRs and pharmacovigilance. Other question items evaluated attitudes toward ADR reporting and ADR reporting practice. The data were summarised using descriptive statistics, while the chi-square test was used to assess categorical variables at p < 0.05. The overall percent score in the knowledge and attitude domains was divided into groups of "poor", "moderate", and "good" knowledge, as well as "positive" and "negative" attitudes. Results: While having a generally poor understanding, this study demonstrates that Lithuanian consumers have a favourable attitude toward pharmacovigilance, particularly regarding issues involving the requirement for reporting. The data also revealed the justifications for reporting and not reporting ADRs. Conclusions: The current study provided the first understanding of consumer awareness and ADR reporting intentions, which can help to develop educational campaigns and interventions addressing pharmacovigilance and ADR reporting.

Cyano-Phycocyanin: Mechanisms of Action on Human Skin and Future Perspectives in Medicine.

Cyano-phycocyanin is one of the active pigments of the blue-green algae and is usually isolated from the filamentous cyanobacteria Arthrospira platensis Gomont (Spirulina). Due to its multiple physiological functions and non-toxicity, cyano-phycocyanin may be a potential substance for the topical treatment of various skin diseases. Considering that the conventional medicine faces drug resistance, insufficient efficacy and side effects, the plant origin compounds can act as an alternative option. Thus, the aim of this paper was to review the wound healing, antimicrobial, antioxidative, anti-inflammatory, antimelanogenic and anticancer properties and mechanisms of cyano-phycocyanin topical activities on human skin. Moreover, possible applications and biotechnological requirements for pharmaceutical forms of cyano-phycocyanin for the treatment of various skin diseases are discussed in this review.

Coagulation System Disorders and Thrombosis Prophylaxis During Laparoscopic Fundoplications.

BACKGROUND: The aim of this study was to assess and recommend the optimal deep vein thrombosis (DVT) prophylaxis regimen during and after laparoscopic fundoplication according to the blood coagulation disorders and the rate of DVT in 2 patient groups, receiving different DVT prophylaxis regimens. MATERIALS AND METHODS: This was a prospective randomized, single-center clinical study. The study population, 121 patients, were divided into 2 groups: group I received low-molecular-weight heparin 12 hours before the operation; group II received low-molecular-weight heparin only 1 hour before the laparoscopic fundoplication. Both groups received intermittent pneumatic compression during the entire procedure. Bilateral Doppler ultrasound to exclude DVT was performed before the surgery. Venous phase computed tomographic images were acquired from the ankle to the iliac tubercles on the third postoperative day to determine the presence and location of DVT. Hypercoagulation state was assessed by measuring the prothrombin fragment F1+2 (F1+2), the thrombin-antithrombin complex (TAT), and tissue factor microparticles activity (MP-TF) in plasma. The hypocoagulation effect was evaluated by measuring plasma free tissue factor pathway inhibitor (fTFPI). RESULTS: F1+2, TAT, and MP-TF indexes increased significantly, whereas fTFPI levels decreased significantly during and after laparoscopic fundoplication, when molecular-weight heparin was administered 12 hours before the operation. Computed tomography venography revealed peroneal vein thrombosis in 2 group I patients on the third postoperative day. Total postsurgical DVT frequency was 1.65%: 3.6% in group I, with no DVT in group II. CONCLUSION: Molecular-weight heparin and intraoperative intermittent pneumatic compression controls the hypercoagulation effect more efficiently when it is administered 1 hour before surgery: it causes significant reduction of F1+2, TAT, and MP-TF indexes and significant increases of fTFPI levels during and after laparoscopic fundoplication.

Comparison of aqueous, polyethylene glycol-aqueous and ethanolic propolis extracts: antioxidant and mitochondria modulating properties.

BACKGROUND: Propolis is multicomponent substance collected by honeybees from various plants. It is known for numerous biological effects and is commonly used as ethanolic extract because most of active substances of propolis are ethanol-soluble. However, water-based propolis extracts could be applied more safely, as this solvent is more biocompatible. On the other hand, water extracts has significantly smaller range and quantity of active compounds. The extraction power of water could be enhanced by adding co-solvent which increases both solubility and penetration of propolis compounds. However, variation of solvents results in different composition of active substances that might have distinct effects. The majority of biological effects of propolis are attributed to the antioxidant properties of its active compounds. Antioxidant effect might be a result of either direct scavenging of ROS or modulation of ROS producing organelle activity. Therefore, the aim of this study was to investigate and compare chemical composition, antioxidant properties and effects on mitochondrial respiration of aqueous (AqEP), polyethylene glycol-aqueous (Pg-AqEP) and ethanolic (EEP) propolis extracts. METHODS: Chemical composition of propolis extracts was determined using HPLC and Folin-Ciocalteu method. Ability to neutralize H2O2 and intracellular ROS concentration in C6 glioma cells were determined fluorometrically by using 10-acetyl-3,7-dihydroxyphenoxazine and 2',7'-dichlorofluorescein diacetate, respectively. Mitochondrial superoxide generation was assessed under fluorescent microscope by using MitoSOX Red. Oxygen uptake rates of mitochondria were recorded by high-resolution respirometer Oxygraph-2 k. RESULTS: Our data revealed that phenolic acids and aldehydes make up 40-42% of all extracted and identified compounds in AqEP and Pg-AqEP and only 16% in EEP. All preparations revealed similar antioxidant activity in cell culture medium but Pg-AqEP and EEP demonstrated better mitochondrial superoxide and total intracellular ROS decreasing properties. At higher concentrations, AqEP and EEP inhibited mitochondrial respiration, but Pg-AqEP had concentration-dependent mitochondria-uncoupling effect. CONCLUSIONS: Aqueous and non-aqueous propolis extracts differ by composition, but all of them possess antioxidant properties and neutralize H2O2 in solution at similar efficiency. However, both Pg-AqEP and EEP were more effective in decreasing intracellular and intramitochondrial ROS compared to AqEP. At higher concentrations, these preparations affect mitochondrial functions and change energy production in C6 cells.

Thromboelastographic changes during laparoscopic fundoplication.

INTRODUCTION: Thromboelastography (TEG) is a technique that measures coagulation processes and surveys the properties of a viscoelastic blood clot, from its formation to lysis. AIM: To determine the possible hypercoagulability state and the effect of antithrombotic prophylaxis on thromboelastogram results and development of venous thrombosis during laparoscopic fundoplication. MATERIAL AND METHODS: The study was performed on 106 patients who were randomized into two groups. The first group received low-molecular-weight heparin (LMWH) 12 h before the operation, and 6 and 30 h after it. The second group received LMWH only 1 h before the laparoscopic fundoplication. The TEG profile was collected before LMWH injection, 1 h after the introduction of the laparoscope and 15 min after the surgery was completed. RESULTS: There was no significant difference in thromboelastography R-time between the groups before low-molecular-weight heparin injection. In group I preoperative R-values significantly decreased 1 h after the introduction of the laparoscope, after the end of surgery and on the third postoperative day. K-time values decreased significantly on the third postoperative day compared with the results before low-molecular-weight heparin injection, and after the operation. In group II, preoperative R-values significantly decreased 1 h after the introduction of the laparoscope, and after surgery. K-time values did not change significantly during or after the laparoscopic operation. CONCLUSIONS: Our study results demonstrated that the hypercoagulation state (according to the TEG results) was observed during and after laparoscopic fundoplication in patients when LMWH was administered 12 h before the operation together with intraoperative intermittent pneumatic compression. The optimal anticoagulation was obtained when LMWH was administered 1 h before fundoplication.

Thrombotic risk assessment in 185 WHO-defined essential thrombocythemia patients: single center experience.

Thrombosis risk in essential thrombocythemia (ET) patients can be assessed using different prognostic systems. Conventional risk factors include age more than 60 years and history of previous thrombosis. In addition, other factors such as JAK2 V617F mutations, cardiovascular risk factors, leukocytosis more than 11 × 10(9)/l, thrombophilic factors and platelet count more than 1500 × 10(9)/l are used in different hematology centers as high-risk features for thrombosis. Our study compared different risk model groups for thrombosis in 185 WHO-defined ET patients at the Hospital of Lithuanian University of Health Sciences Kaunas Klinikos. We found that patient distribution in low, intermediate- and high-risk groups varies using different risk stratification models. The biggest difference in risk assignment is evident in patients who are older than 60 years and have no other risk factors and in patients who are younger than 60 years but have other risk factors. This observation suggests that new prospective randomized clinical trials are needed to better stratify patients at risk for thrombosis.

A combinative effect of low-molecular-weight heparin and intermittent pneumatic compression device for thrombosis prevention during laparoscopic fundoplication.

BACKGROUND. Venous thromboembolism is known to be an important social and health care problem because of its high incidence among patients who undergo surgery. For instance, 20-30% of patients develop this problem after general surgical operations, while 5.5% of patients have this complication when laparoscopic fundoplications are performed without any prophylaxis. The aim of our study was to evaluate the hypocoagulation effect of the following treatments during and after laparoscopic fundoplication: a) intermittent pneumatic compression (IPC) and b) combination of low-molecular-weight heparin (LMWH) and IPC. MATERIAL AND METHODS. The study was performed on 20 consecutive patients who were randomized into two groups. The first group received IPC during operation, the second group received IPC during operation and LMWH before operation. Plasma prothrombin fragment F1+2 (F1+2), thrombin-antithrombin complex (TAT) - markers of thrombogenesis - and plasma free tissue factor pathway inhibitor (fTFPI) - a marker of hypocoagulation effect - were measured 1 h before, during, and after the laparoscopic operation. RESULTS. In the IPC group, plasma F1+2 and TAT levels increased significantly during and after laparoscopic gastrofundoplication. In the IPC+LMWH group, F1+2 and plasma TAT levels did not change during or after the operation. fTFPI levels significantly increased during and after the operation in the IPC+LMWH group; however, fTFPI levels did not change during or after the laparoscopic operation in the IPC group. CONCLUSIONS. A combination of low-molecular-weight heparin and intermittent pneumatic compression during laparoscopic fundoplication caused hypocoagulation effect in the patients, which was not observed in the patients who were treated with intermittent pneumatic compression alone.

Differential effects of DX-9065a, argatroban, and synthetic pentasaccharide on tissue thromboplastin inhibition test and dilute Russell's viper venom test.

New synthetic direct and indirect factor Xa or factor IIa inhibitors are increasingly used for the prevention and treatment of thrombotic disorders, including patients suffering from antiphospholipid syndrome. In this study, the effects of the synthetic direct factor Xa inhibitor DX-9065a, the indirect synthetic heparinomimetic pentasaccharide, and the direct factor IIa inhibitor Argatroban were studied. These two widely used assays for the detection of lupus anticoagulant, namely the tissue thromboplastin inhibition (TTIT) and the dilute Russell viper venom tests (DRWT) proved useful. The drugs were added to a normal human plasma pool ranging in concentration from 0.04 to 10 microg/mL. Using the two tests named above, DX-9065a and Argatroban showed a dose-related prolongation of TTIT and DRWT in the concentration range from 0.04 to 5 micromol/mL, but the pentasaccharide only slightly prolonged the clotting times of these assays even at high concentrations. Argatroban had the more pronounced effect on both tests when compared with DX-9065a (p < 0.001). The most responsive assay for DX-9065a up to a concentration of 2.5 micromol/mL was the DRWT. For Argatroban both TTIT and DRWT were equally responsive. Patients whose plasma was tested for suspected lupus anticoagulant and who have been given DX-9065a or Argatroban may have false-positive results with the TTIT tests and DRWT. This effect should be considered during patient management. These results indicate that these assays could be used for the effective quantitation of the direct factor Xa or factor IIa inhibitors when suitable controls are used.

[Study of biopharmaceutic characteristics of cromoglycate eye drops]. / Natrio kromoglikato akiu lasu biofarmaciniu charakteristiku tyrimas.

One of the factors influencing the release of active substance from the drug formulation is presence of polymeric substance resulting in increase of viscosity of eye drops. Diffusion of sodium cromoglycate from polyvinyl alcohol 1.4%, 3% solutions and hypromellose 1% aqueous solution was investigated using in vitro method and diffusion coefficients were evaluated. Release of sodium cromoglycate from polyvinyl alcohol 1.4%, 3% solutions and hypromellose 1% aqueous solution was slower than the release from aqueous solution of sodium cromoglycate. The sodium cromoglycate diffusion from ophthalmic vehicle process kinetics was influenced by viscosity of these solutions and nature of the used polymers. The diffusion process of sodium cromoglycate from 1.4% PVA solution was more intensive if compared to diffusion from 1% hypromellose solution. The influence of excipients on sodium cromoglycate diffusion from eye drop formulation was evaluated when polymeric solutions have been used as vehicles.

[Development of formulations of desmopressin intranasal drops]. / Dezmopresino intranazaliniu lasu technologijos sukurimas.

In recent years synthetic vasopressin analogues (particularly desmopressin) emerged as safe and effective representatives of this class of drugs for same clinical indications as natural hormone. It was imperative to create intranasal drug form using synthetic desmopressin compound. The purpose of this work was to develop formulations of intranasal desmopressin drug using synthetic active compound with optimal composition. Aquatic desmopressin intranasal solution was prepared in 0.05 mg/ml concentration using phosphate buffer (pH 4.5-5.5) and following preservatives: nipagin-nipazol 7:3--0.1% or benzalkonium chloride 0.01%. Sterility is the main condition for intranasal drops and hormones as a raw material are thermolabile so it is not possible to apply a thermic sterilisation. Polymeric membrane filters of 0.22 micron pore size were employed as sterilizing filters. In order to control the quality, to determine the stability of desmopressin intranasal drops at long-lasting storage (24 months) and to evaluate the influence of the technological factors we have developed the analytical methods of quality control. According to our quality control data, desmopressin intranasal drops are stable for two years and remain sterile during storage and administration of the drug.